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Stage 5 chronic kidney disease

MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome; Finding
Synonyms: End-stage renal disease; Renal failure, endstage
SNOMED CT: Chronic kidney disease stage 5 (433146000); CKD stage 5 (433146000)
 
HPO: HP:0003774
Monarch Initiative: MONDO:0004375

Definition

A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVStage 5 chronic kidney disease

Conditions with this feature

Lowe syndrome
MedGen UID:
18145
Concept ID:
C0028860
Disease or Syndrome
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including low molecular-weight (LMW) proteinuria, aminoaciduria, bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, hypercalciuria, sodium and potassium wasting, and polyuria. The features of symptomatic Fanconi syndrome do not usually become manifest until after the first few months of life, except for LMW proteinuria. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease between the second and fourth decades of life.
Familial Mediterranean fever
MedGen UID:
45811
Concept ID:
C0031069
Disease or Syndrome
Familial Mediterranean fever (FMF) is divided into two phenotypes: type 1 and type 2. FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis and meningitis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication, if untreated. FMF type 2 is characterized by amyloidosis as the first clinical manifestation of FMF in an otherwise asymptomatic individual.
Primary hypomagnesemia
MedGen UID:
120640
Concept ID:
C0268448
Disease or Syndrome
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a progressive renal disorder characterized by excessive urinary Ca(2+) and Mg(2+) excretion. There is progressive loss of kidney function, and in about 50% of cases, the need for renal replacement therapy arises as early as the second decade of life (summary by Muller et al., 2006). Amelogenesis imperfecta may also be present in some patients (Bardet et al., 2016). A similar disorder with renal magnesium wasting, renal failure, and nephrocalcinosis (HOMG5; 248190) is caused by mutations in another tight-junction gene, CLDN19 (610036), and is distinguished by the association of severe ocular involvement. For a discussion of phenotypic and genetic heterogeneity of familial hypomagnesemia, see HOMG1 (602014).
Juvenile nephropathic cystinosis
MedGen UID:
75701
Concept ID:
C0268626
Congenital Abnormality
Cystinosis comprises three allelic phenotypes: Nephropathic cystinosis in untreated children is characterized by renal Fanconi syndrome, poor growth, hypophosphatemic/calcipenic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine in almost all cells, leading to cellular dysfunction with tissue and organ impairment. The typical untreated child has short stature, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these interventions, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized clinically only by photophobia resulting from corneal cystine crystal accumulation.
Lysinuric protein intolerance
MedGen UID:
75704
Concept ID:
C0268647
Disease or Syndrome
Lysinuric protein intolerance (LPI) typically presents after an infant is weaned from breast milk or formula; variable findings include recurrent vomiting and episodes of diarrhea, episodes of stupor and coma after a protein-rich meal, poor feeding, aversion to protein-rich food, failure to thrive, hepatosplenomegaly, and muscular hypotonia. Over time, findings include: poor growth, osteoporosis, involvement of the lungs (progressive interstitial changes, pulmonary alveolar proteinosis) and of the kidneys (progressive glomerular and proximal tubular disease), hematologic abnormalities (normochromic or hypochromic anemia, leukopenia, thrombocytopenia, erythroblastophagocytosis in the bone marrow aspirate), and a clinical presentation resembling the hemophagocytic lymphohistiocytosis/macrophagic activation syndrome. Hypercholesterolemia, hypertriglyceridemia, and acute pancreatitis can also be seen.
Progressive hereditary glomerulonephritis without deafness
MedGen UID:
98012
Concept ID:
C0403443
Disease or Syndrome
A rare, genetic hypertension characterized by an adult onset of increased blood pressure associated with nephropathy progressing to end-stage renal disease. Renal biopsy may show interstitial fibrosis, glomerulosclerosis and mild tubular atrophy. Increased serum creatinine and proteinuria have also been reported.
Nail-patella-like renal disease
MedGen UID:
140789
Concept ID:
C0403548
Disease or Syndrome
Focal segmental glomerulosclerosis-10 (FSGS10) is an autosomal dominant kidney disease characterized by isolated glomerulopathy without extrarenal manifestations. In particular, affected individuals do not have other signs of NPS. The renal disease is highly variable in severity and pathology, even within the same family. Most patients present in the first decades of life with proteinuria and hematuria, although onset of symptoms can manifest at any age, including late adulthood. Some patients progress to end-stage renal disease, whereas others have a stable disease course. Light microscopic analysis of renal biopsies shows a constellation of glomerular abnormalities, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), and, rarely, immune complex nephropathy. Electron microscopy characteristically shows an irregular thickening of the glomerular basement membrane (GBM) with electron-lucent areas containing accumulated bundles of type III collagen fibrils. The collagen deposition usually occurs in endothelial cells of the GBM; partial effacement of podocyte foot processes may also be present. These specific pathologic findings are similar to those observed in NPS patients with nephropathy. However, these findings may not always be present, which may make the diagnosis challenging (summary by Hall et al., 2017, Lei et al., 2020; review by Harita et al., 2017). For a discussion of genetic heterogeneity of FSGS, see FSGS1 (603278).
Glomerulopathy with fibronectin deposits 1
MedGen UID:
98017
Concept ID:
C0403557
Disease or Syndrome
Glomerulopathy with fibronectin deposits (GFND) is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (FN1; 135600) (Castelletti et al., 2008). Genetic Heterogeneity of Glomerulopathy with Fibronectin Deposits The GFND1 locus maps to chromosome 1q32. See also GFND2 (601894), which is caused by mutation in the FN1 gene (135600) on chromosome 2q35.
Renal cysts and diabetes syndrome
MedGen UID:
96569
Concept ID:
C0431693
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Cranioectodermal dysplasia 1
MedGen UID:
96586
Concept ID:
C0432235
Disease or Syndrome
Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
Schimke immuno-osseous dysplasia
MedGen UID:
164078
Concept ID:
C0877024
Congenital Abnormality
Schimke immunoosseous dysplasia (SIOD) is characterized by spondyloepiphyseal dysplasia (SED) resulting in short stature, nephropathy, and T-cell deficiency. Radiographic manifestations of SED include ovoid and mildly flattened vertebral bodies, small ilia with shallow dysplastic acetabular fossae, and small deformed capital femoral epiphyses. Nearly all affected individuals have progressive steroid-resistant nephropathy, usually developing within five years of the diagnosis of growth failure and terminating with end-stage renal disease. The majority of tested individuals have T-cell deficiency and an associated risk for opportunistic infection, a common cause of death. SIOD involves a spectrum that ranges from an infantile or severe early-onset form with a greater risk of death during childhood to a juvenile or milder later-onset form with likely survival into adulthood if renal disease is appropriately treated.
Drash syndrome
MedGen UID:
181980
Concept ID:
C0950121
Disease or Syndrome
WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful.
Frasier syndrome
MedGen UID:
215533
Concept ID:
C0950122
Disease or Syndrome
WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful.
Finnish type amyloidosis
MedGen UID:
301243
Concept ID:
C1622345
Disease or Syndrome
The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported (Meretoja, 1973). Finnish hereditary amyloidosis, also known as Meretoja syndrome or AGel amyloidosis, is one of the most common diseases in the Finnish disease heritage. Symptoms commonly appear by age 40, with the first finding usually corneal lattice dystrophy (CLD), diagnosed by an ophthalmologist. Impaired vision, polyneuropathy, facial nerve paresis, and cutis laxa follow. These symptoms may develop slowly and simultaneously, since amyloid accumulates systemically at a constant rate (summary by Nikoskinen et al., 2015). For a discussion of genetic heterogeneity of hereditary systemic amyloidosis, see AMYLD1 (105210).
Congenital anomalies of kidney and urinary tract 1
MedGen UID:
322763
Concept ID:
C1835826
Congenital Abnormality
Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a broad spectrum of renal and urinary tract malformations. CAKUT structural anomalies range from complete renal agenesis (the most severe), to renal hypodysplasia, multicystic kidney dysplasia, duplex renal collecting system, ureteropelvic junction obstruction (UPJO), megaureter, posterior urethral valves (PUV), and vesicoureteral reflux (VUR). Renal abnormalities are observed in close relatives of up to 10% of CAKUT patients, although these are frequently asymptomatic. The phenotype often does not follow classic mendelian inheritance: family members with the same genetic defect may have variable phenotypes, ranging from severe renal insufficiency to asymptomatic anomalies. CAKUT occurs in about 1 in 500 live births, but are severe enough to cause neonatal death in about 1 in 2,000 births. In addition, CAKUT can occur in syndromic disorders in association with other congenital anomalies, such as papillorenal syndrome (120330) (summary by Renkema et al., 2011). Genetic Heterogeneity of Congenital Anomalies of Kidney and Urinary Tract Also see CAKUT2 (143400), caused by mutation in the TBX18 gene (604613) on chromosome 6q14, and CAKUT3 (618270), caused by mutation in the NRIP1 gene (602490) on chromosome 21q.
Senior-Loken syndrome 5
MedGen UID:
332226
Concept ID:
C1836517
Disease or Syndrome
Senior-Loken syndrome is an autosomal recessive disorder with the main features of nephronophthisis (NPHP; see 256100) and Leber congenital amaurosis (LCA; see 204000). For a general phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Epidermolysis bullosa simplex 7, with nephropathy and deafness
MedGen UID:
323004
Concept ID:
C1836823
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Pierson syndrome
MedGen UID:
373199
Concept ID:
C1836876
Disease or Syndrome
Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).
Joubert syndrome 3
MedGen UID:
332931
Concept ID:
C1837713
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Mandibuloacral dysplasia with type B lipodystrophy
MedGen UID:
332940
Concept ID:
C1837756
Disease or Syndrome
Mandibuloacral dysplasia with type B lipodystrophy (MADB) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies such as mandibular hypoplasia, skeletal anomalies such as progressive osteolysis of the terminal phalanges and clavicles, and skin changes such as mottled hyperpigmentation and atrophy. The lipodystrophy is characterized by generalized loss of subcutaneous fat involving the face, trunk, and extremities. Some patients have a progeroid appearance. Metabolic complications associated with insulin resistance have been reported (Schrander-Stumpel et al., 1992; summary by Simha et al., 2003). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370).
X-linked diffuse leiomyomatosis-Alport syndrome
MedGen UID:
333429
Concept ID:
C1839884
Disease or Syndrome
A rare renal disease characterized by the association of X-linked Alport syndrome (glomerular nephropathy, sensorineural deafness and ocular anomalies) and benign proliferation of visceral smooth muscle cells along the gastrointestinal, respiratory, and female genital tracts and clinically manifests with dysphagia, dyspnea, cough, stridor, postprandial vomiting, retrosternal or epigastric pain, recurrent pneumonia, and clitoral hypertrophy in females.
Joubert syndrome with renal defect
MedGen UID:
335526
Concept ID:
C1846790
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Senior-Loken syndrome 4
MedGen UID:
337697
Concept ID:
C1846979
Disease or Syndrome
Senior-Loken syndrome-4 (SLSN4) is an autosomal recessive disorder characterized by the association of the cystic renal disorder nephronophthisis with late-onset retinitis pigmentosa (Schuermann et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Senior-loken syndrome 3
MedGen UID:
335569
Concept ID:
C1846980
Disease or Syndrome
Senior-Løken syndrome is a rare disorder characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye condition known as Leber congenital amaurosis.\n\nNephronophthisis causes fluid-filled cysts to develop in the kidneys beginning in childhood. These cysts impair kidney function, initially causing increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). Nephronophthisis leads to end-stage renal disease (ESRD) later in childhood or in adolescence. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.\n\nLeber congenital amaurosis primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). Some people with Senior-Løken syndrome develop the signs of Leber congenital amaurosis within the first few years of life, while others do not develop vision problems until later in childhood.
Nephronophthisis 4
MedGen UID:
339667
Concept ID:
C1847013
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Dent disease type 1
MedGen UID:
336322
Concept ID:
C1848336
Disease or Syndrome
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD.
Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction
MedGen UID:
376565
Concept ID:
C1849333
Disease or Syndrome
Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (RCDFRD) is characterized by onset of hearing impairment and reduced vision within the first 5 years of life. Renal dysfunction results in rickets-like skeletal changes, and death may occur in childhood or young adulthood due to renal failure (Beighton et al., 1993).
Saldino-Mainzer syndrome
MedGen UID:
341455
Concept ID:
C1849437
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Renal coloboma syndrome
MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal coloboma syndrome and characterized by renal hypodysplasia and abnormalities of the optic nerve; with improved access to molecular testing, a wider range of phenotypes has been recognized in association with pathogenic variants in PAX2. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77% of affected individuals. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency / renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Uric acid nephrolithiasis has been reported. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with PAX2–related disorder. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity. PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis.
Nephrotic syndrome, type 3
MedGen UID:
377831
Concept ID:
C1853124
Disease or Syndrome
Nephrotic syndrome, a malfunction of the glomerular filter, is characterized clinically by proteinuria, edema, and end-stage renal disease (ESRD). Renal histopathology may show diffuse mesangial sclerosis (DMS) or focal segmental glomerulosclerosis (FSGS) (Hinkes et al., 2006). Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen (Gbadegesin et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Joubert syndrome 6
MedGen UID:
342805
Concept ID:
C1853153
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
MedGen UID:
344424
Concept ID:
C1855114
Disease or Syndrome
For this GeneReview, the term "isolated methylmalonic acidemia" refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood and urine that result from the failure to isomerize (convert) methylmalonyl-coenzyme A (CoA) into succinyl-CoA during propionyl-CoA metabolism in the mitochondrial matrix, without hyperhomocysteinemia or homocystinuria, hypomethioninemia, or variations in other metabolites, such as malonic acid. Isolated MMA is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, 5-deoxy-adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Prior to the advent of newborn screening, common phenotypes included: Infantile/non-B12-responsive form (mut0 enzymatic subtype, cblB), the most common phenotype, associated with infantile-onset lethargy, tachypnea, hypothermia, vomiting, and dehydration on initiation of protein-containing feeds. Without appropriate treatment, the infantile/non-B12-responsive phenotype could rapidly progress to coma due to hyperammonemic encephalopathy. Partially deficient or B12-responsive phenotypes (mut– enzymatic subtype, cblA, cblB [rare], cblD-MMA), in which symptoms occur in the first few months or years of life and are characterized by feeding problems, failure to thrive, hypotonia, and developmental delay marked by episodes of metabolic decompensation. Methylmalonyl-CoA epimerase deficiency, in which findings range from complete absence of symptoms to severe metabolic acidosis. Affected individuals can also develop ataxia, dysarthria, hypotonia, mild spastic paraparesis, and seizures. In those individuals diagnosed by newborn screening and treated from an early age, there appears to be decreased early mortality, less severe symptoms at diagnosis, favorable short-term neurodevelopmental outcome, and lower incidence of movement disorders and irreversible cerebral damage. However, secondary complications may still occur and can include intellectual disability, tubulointerstitial nephritis with progressive impairment of renal function, "metabolic stroke" (bilateral lacunar infarction of the basal ganglia during acute metabolic decompensation), pancreatitis, growth failure, functional immune impairment, bone marrow failure, optic nerve atrophy, arrhythmias and/or cardiomyopathy (dilated or hypertrophic), liver steatosis/fibrosis/cancer, and renal cancer.
Joubert syndrome with oculorenal defect
MedGen UID:
340930
Concept ID:
C1855675
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Nephronophthisis 1
MedGen UID:
343406
Concept ID:
C1855681
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Senior-Loken syndrome 6
MedGen UID:
387907
Concept ID:
C1857779
Disease or Syndrome
Senior-Loken syndrome-6 (SLSN6) is an autosomal recessive disorder characterized by the association of nephronophthisis resulting in end-stage renal disease in the second decade of life with retinal degeneration (Sayer et al., 2006). For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Joubert syndrome 5
MedGen UID:
347545
Concept ID:
C1857780
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Nephronophthisis 3
MedGen UID:
346809
Concept ID:
C1858392
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Focal segmental glomerulosclerosis 2
MedGen UID:
349053
Concept ID:
C1858915
Disease or Syndrome
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (review by Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome (NPHS), see FSGS1 (603278).
Infantile nephronophthisis
MedGen UID:
355574
Concept ID:
C1865872
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Glomerulopathy with fibronectin deposits 2
MedGen UID:
356149
Concept ID:
C1866075
Disease or Syndrome
Glomerulopathy with fibronectin deposits is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (Castelletti et al., 2008). For a discussion of genetic heterogeneity of GFND, see 137950.
Tubulointerstitial kidney disease, autosomal dominant, 2
MedGen UID:
358137
Concept ID:
C1868139
Disease or Syndrome
Autosomal dominant tubulointerstitial kidney disease – MUC1 (ADTKD-MUC1) is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. The rate of loss of kidney function for individuals is variable within and between families, with a median age of onset of end-stage renal disease (ESRD) of 46 years (range: ages 20-70 years). There are no other systemic manifestations.
Nephrotic syndrome, type 2
MedGen UID:
358380
Concept ID:
C1868672
Disease or Syndrome
Steroid-resistant nephrotic syndrome type 2 is an autosomal recessive disorder characterized clinically by childhood onset of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. The disorder is resistant to steroid treatment and progresses to end-stage renal failure in the first or second decades (summary by Fuchshuber et al., 1996). Some patients show later onset of the disorder (Tsukaguchi et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Alagille syndrome due to a JAG1 point mutation
MedGen UID:
365434
Concept ID:
C1956125
Disease or Syndrome
Alagille syndrome (ALGS) is a multisystem disorder with a wide spectrum of clinical variability; this variability is seen even among individuals from the same family. The major clinical manifestations of ALGS are bile duct paucity on liver biopsy, cholestasis, congenital cardiac defects (primarily involving the pulmonary arteries), butterfly vertebrae, ophthalmologic abnormalities (most commonly posterior embryotoxon), and characteristic facial features. Renal abnormalities, growth failure, developmental delays, splenomegaly, and vascular abnormalities may also occur.
Joubert syndrome 7
MedGen UID:
369401
Concept ID:
C1969053
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Nephronophthisis 7
MedGen UID:
369409
Concept ID:
C1969092
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
NPHP3-related Meckel-like syndrome
MedGen UID:
382217
Concept ID:
C2673885
Disease or Syndrome
This autosomal recessive disorder is designated Meckel syndrome type 7 (MKS7) based on the classic phenotypic triad of (1) cystic renal disease; (2) a central nervous system abnormality, and (3) hepatic abnormalities, as defined by Meckel (1822), Salonen (1984), and Logan et al. (2011). According to these criteria, polydactyly is a variable feature. Herriot et al. (1991) and Al-Gazali et al. (1996) concluded that Dandy-Walker malformation can be the phenotypic manifestation of a central nervous system malformation in MKS. For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Multicentric carpo-tarsal osteolysis with or without nephropathy
MedGen UID:
436237
Concept ID:
C2674705
Disease or Syndrome
Multicentric carpotarsal osteolysis syndrome is a rare skeletal disorder, usually presenting in early childhood with a clinical picture mimicking juvenile rheumatoid arthritis. Progressive destruction of the carpal and tarsal bone usually occurs and other bones may also be involved. Chronic renal failure is a frequent component of the syndrome. Mental retardation and minor facial anomalies have been noted in some patients. Autosomal dominant inheritance has been documented in many families (Pai and Macpherson, 1988). See also Torg-Winchester syndrome (259600), an autosomal recessive multicentric osteolysis syndrome.
Focal segmental glomerulosclerosis 4, susceptibility to
MedGen UID:
390820
Concept ID:
C2675525
Finding
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Joubert syndrome 9
MedGen UID:
382940
Concept ID:
C2676788
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Focal segmental glomerulosclerosis 5
MedGen UID:
413315
Concept ID:
C2750475
Disease or Syndrome
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). Dominant intermediate Charcot-Marie-Tooth disease E and focal segmental glomerulonephritis (CMTDIE; 614455) is also caused by heterozygous mutation in the INF2 gene. For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Polycystic kidney disease 2
MedGen UID:
442699
Concept ID:
C2751306
Disease or Syndrome
Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral kidney cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Kidney manifestations include early-onset hypertension, kidney pain, and kidney insufficiency. Approximately 50% of individuals with ADPKD have end-stage kidney disease (ESKD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD), most often in females. Overall, the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of kidney disease and other extra-kidney manifestations.
Atypical hemolytic-uremic syndrome with C3 anomaly
MedGen UID:
442875
Concept ID:
C2752037
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD).
Nephropathic cystinosis
MedGen UID:
419735
Concept ID:
C2931187
Disease or Syndrome
Cystinosis comprises three allelic phenotypes: Nephropathic cystinosis in untreated children is characterized by renal Fanconi syndrome, poor growth, hypophosphatemic/calcipenic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine in almost all cells, leading to cellular dysfunction with tissue and organ impairment. The typical untreated child has short stature, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these interventions, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized clinically only by photophobia resulting from corneal cystine crystal accumulation.
Nephronophthisis-like nephropathy 1
MedGen UID:
461769
Concept ID:
C3150419
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Fanconi anemia complementation group O
MedGen UID:
462003
Concept ID:
C3150653
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA.
Immunodeficiency, common variable, 6
MedGen UID:
462091
Concept ID:
C3150741
Disease or Syndrome
Any common variable immunodeficiency in which the cause of the disease is a mutation in the CD81 gene.
Nephronophthisis 11
MedGen UID:
462146
Concept ID:
C3150796
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Asphyxiating thoracic dystrophy 4
MedGen UID:
462535
Concept ID:
C3151185
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Nephronophthisis 12
MedGen UID:
462536
Concept ID:
C3151186
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Nephronophthisis 9
MedGen UID:
462538
Concept ID:
C3151188
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
IgA nephropathy, susceptibility to, 2
MedGen UID:
462728
Concept ID:
C3151378
Finding
IgA nephropathy, susceptibility to, 1
MedGen UID:
463619
Concept ID:
C3160719
Finding
Cranioectodermal dysplasia 3
MedGen UID:
481437
Concept ID:
C3279807
Disease or Syndrome
Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
Focal segmental glomerulosclerosis 6
MedGen UID:
481535
Concept ID:
C3279905
Disease or Syndrome
Focal segmental glomerulosclerosis-6 is an autosomal recessive childhood-onset kidney disorder manifest clinically by the nephrotic syndrome, which is characterized by proteinuria, hematuria, hypoalbuminemia, and progressive renal failure. It is a disease of the glomerular podocyte (summary by Mele et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Nephrotic syndrome, type 6
MedGen UID:
481730
Concept ID:
C3280100
Disease or Syndrome
The nephrotic syndrome refers to a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema, resulting in end-stage kidney disease if untreated. Inherited defects in podocyte structure and function have been observed in some children with the steroid-resistant subtype of nephrotic syndrome (summary by Ozaltin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
LAMB2-related infantile-onset nephrotic syndrome
MedGen UID:
481743
Concept ID:
C3280113
Disease or Syndrome
Nephrotic syndrome type 5 (NPHS5) is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus (summary by Hasselbacher et al., 2006). Mutation in the LAMB2 gene can also cause Pierson syndrome (609049), which is characterized by nephrotic syndrome, distinct ocular anomalies, namely microcoria, and neurodevelopmental delay. For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Asphyxiating thoracic dystrophy 5
MedGen UID:
482228
Concept ID:
C3280598
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Nephronophthisis 13
MedGen UID:
482242
Concept ID:
C3280612
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Cranioectodermal dysplasia 4
MedGen UID:
482246
Concept ID:
C3280616
Disease or Syndrome
Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
Chromosome 17q12 deletion syndrome
MedGen UID:
482768
Concept ID:
C3281138
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Familial steroid-resistant nephrotic syndrome with sensorineural deafness
MedGen UID:
766263
Concept ID:
C3553349
Disease or Syndrome
Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen.
Karyomegalic interstitial nephritis
MedGen UID:
766688
Concept ID:
C3553774
Disease or Syndrome
Karyomegalic tubulointerstitial nephritis (KMIN) is a rare kidney disease characterized clinically by onset in the third decade of progressive renal failure. Renal biopsy shows chronic tubulointerstitial nephritis and interstitial fibrosis associated with enlarged and atypical tubular epithelial cell nuclei (summary by Baba et al., 2006).
Immunoglobulin-mediated membranoproliferative glomerulonephritis
MedGen UID:
767244
Concept ID:
C3554330
Disease or Syndrome
C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity.
Bardet-Biedl syndrome 17
MedGen UID:
811538
Concept ID:
C3714980
Disease or Syndrome
Bardet-Biedl syndrome-17 (BBS17) is an autosomal recessive ciliopathy characterized by retinitis pigmentosa, cognitive impairment, obesity, renal dysfunction, and hypogenitalism. Polydactyly, most often postaxial, is also a primary feature of BBS; in BBS17, mesoaxial polydactyly, with fused or Y-shaped metacarpals, is a distinct manifestation (Deffert et al., 2007; Schaefer et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Renal-hepatic-pancreatic dysplasia 1
MedGen UID:
811626
Concept ID:
C3715199
Disease or Syndrome
Any renal-hepatic-pancreatic dysplasia in which the cause of the disease is a mutation in the NPHP3 gene.
Bardet-Biedl syndrome 18
MedGen UID:
812504
Concept ID:
C3806174
Disease or Syndrome
BBS18 is an autosomal recessive ciliopathy characterized by retinitis pigmentosa, obesity, kidney failure, and cognitive disability (Scheidecker et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Nephrotic syndrome, type 8
MedGen UID:
815283
Concept ID:
C3808953
Disease or Syndrome
Any nephrotic syndrome in which the cause of the disease is a mutation in the ARHGDIA gene.
Nephronophthisis 16
MedGen UID:
815650
Concept ID:
C3809320
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
MedGen UID:
816258
Concept ID:
C3809928
Disease or Syndrome
Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
Nephrotic syndrome, type 9
MedGen UID:
816295
Concept ID:
C3809965
Disease or Syndrome
Nephrotic syndrome type 9 (NPHS9) is an autosomal recessive chronic kidney disorder characterized by significant proteinuria resulting in hypoalbuminemia and edema. Onset is in the first or second decade of life. The disorder is steroid treatment-resistant and usually progresses to end-stage renal disease requiring transplantation. Renal biopsy shows focal segmental glomerulosclerosis (FSGS) or collapsing FSGS (summary by Ashraf et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Bardet-Biedl syndrome 16
MedGen UID:
855172
Concept ID:
C3889474
Disease or Syndrome
Bardet-Biedl syndrome-16 (BBS16) is an autosomal recessive ciliopathy characterized by retinal degeneration, obesity, renal disease, and cognitive impairment. Although polydactyly is considered a primary feature of BBS overall, it has not been reported in any BBS16 patient (Billingsley et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Nephronophthisis 18
MedGen UID:
855697
Concept ID:
C3890591
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Focal segmental glomerulosclerosis 7
MedGen UID:
863362
Concept ID:
C4014925
Disease or Syndrome
Focal segmental glomerulosclerosis is a form of kidney injury defined by partial sclerosis of some, but not all, glomeruli. It is characterized clinically by significant proteinuria with or without features of nephrotic syndrome. Some patients develop end-stage renal disease (summary by Barua et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Focal segmental glomerulosclerosis 8
MedGen UID:
863430
Concept ID:
C4014993
Disease or Syndrome
Any focal segmental glomerulosclerosis in which the cause of the disease is a mutation in the ANLN gene.
Nephronophthisis 19
MedGen UID:
863979
Concept ID:
C4015542
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
C3 glomerulonephritis
MedGen UID:
884569
Concept ID:
C4055342
Disease or Syndrome
C3 glomerulopathy-3 (C3G3) is an autosomal dominant kidney disease characterized by the onset of microscopic or macroscopic hematuria in the first 3 decades of life, followed by variable progression of renal disease. After age 30, about half of patients continue to have episodic hematuria while maintaining normal renal function, whereas the other half develop proteinuria and progressive renal failure or end-stage renal disease. In some cases, renal dysfunction may be triggered or exacerbated by an infectious disease, often an upper respiratory infection or pharyngitis. Some patients may also develop hypertension. Renal biopsy shows glomerular C3 deposition and mesangial proliferation with glomerulonephritis. Membranoproliferative glomerulonephritis (MPGN) may also be observed on renal biopsy. Males tend to have a more severe phenotype than females and are more likely to develop end-stage renal disease, often necessitating dialysis or renal transplant (summary by Athanasiou et al., 2011). For a general description and discussion of genetic heterogeneity of C3G, see C3G1 (609814).
Nephrotic syndrome, type 13
MedGen UID:
900240
Concept ID:
C4225165
Disease or Syndrome
Nephrotic syndrome type 13 is a steroid-resistant form of nephrotic syndrome with focal segmental glomerulosclerosis (Braun et al., 2016).
Nephrotic syndrome, type 12
MedGen UID:
904365
Concept ID:
C4225166
Disease or Syndrome
Nephrotic syndrome type 12 (NPHS12) is an autosomal recessive renal disorder caused by defects in the renal glomerular filter. Affected individuals have onset of progressive renal failure in the first years of life. Renal biopsy typically shows focal segmental glomerulosclerosis (FSGS) (summary by Braun et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
IgA nephropathy, susceptibility to, 3
MedGen UID:
897340
Concept ID:
C4225194
Finding
Any IgA glomerulonephritis in which the cause of the disease is a mutation in the SPRY2 gene.
Nephrotic syndrome, type 11
MedGen UID:
898622
Concept ID:
C4225228
Disease or Syndrome
Nephrotic syndrome type 11 (NPHS11) is an autosomal recessive disorder of the kidney with onset in the first decade of life. The disorder is progressive and usually results in end-stage renal disease necessitating renal transplantation, although some patients may have a slightly milder phenotype (Miyake et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Senior-Loken syndrome 9
MedGen UID:
899086
Concept ID:
C4225263
Disease or Syndrome
Senior-Loken syndrome-9 is an autosomal recessive disorder characterized by early-onset nephronophthisis and pigmentary retinopathy. Additional more variable features can include liver defects, skeletal anomalies, and obesity (summary by Bizet et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Senior-Loken syndrome 8
MedGen UID:
905171
Concept ID:
C4225376
Disease or Syndrome
Any Senior-Loken syndrome in which the cause of the disease is a mutation in the WDR19 gene.
Charcot-Marie-Tooth disease dominant intermediate E
MedGen UID:
928336
Concept ID:
C4302667
Disease or Syndrome
Autosomal dominant intermediate Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis is characterized by the neurologic features of CMT, including distal muscle weakness and atrophy and distal sensory loss, and the features of FSGS, including proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy (summary by Boyer et al., 2011). Isolated focal segmental glomerulosclerosis-5 (FSGS5; 613237) is also caused by heterozygous mutation in the INF2 gene. For a discussion of genetic heterogeneity of CMTDI, see 606482.
Nephronophthisis 20
MedGen UID:
934607
Concept ID:
C4310640
Disease or Syndrome
Nephronophthisis-20 (NPHP20) is an autosomal recessive tubulointerstitial nephritis characterized by progressive renal fibrosis resulting in end-stage renal failure. The age at onset is relatively late compared to other forms of NPHP, and patients develop end-stage renal disease in the second or third decades. Unlike most other forms of NPHP, NPHP20 does not have features of a ciliopathy and patients do not appear to have extrarenal manifestations (summary by Macia et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100).
Galloway-Mowat syndrome 2, X-linked
MedGen UID:
1625619
Concept ID:
C4538784
Disease or Syndrome
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Nephrotic syndrome 15
MedGen UID:
1620414
Concept ID:
C4539896
Disease or Syndrome
NPHS15 is an autosomal recessive renal disorder characterized by onset of impaired kidney function with proteinuria in the first months of life. The disease course and severity varies widely. Some patients show rapid progression to end-stage renal failure necessitating transplant, whereas others have a more benign course that can be managed with medication. Renal biopsy tends to show glomerular sclerosis and effacement of podocyte foot processes (summary by Bierzynska et al., 2017). For a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Polycystic kidney disease 5
MedGen UID:
1624679
Concept ID:
C4539903
Disease or Syndrome
PKD5, a form of autosomal recessive polycystic kidney disease (ARPKD), is characterized by early childhood onset of progressive renal dysfunction associated with enlarged hyperechogenic kidneys that often results in end-stage renal disease in the second or third decade of life. Arterial hypertension is apparent in early childhood (summary by Lu et al., 2017). For a discussion of genetic heterogeneity of polycystic kidney disease, see PKD1 (173900).
Galloway-Mowat syndrome 3
MedGen UID:
1627611
Concept ID:
C4540266
Disease or Syndrome
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Galloway-Mowat syndrome 4
MedGen UID:
1613511
Concept ID:
C4540270
Disease or Syndrome
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Galloway-Mowat syndrome 5
MedGen UID:
1617227
Concept ID:
C4540274
Disease or Syndrome
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism and ear abnormalities. Other features, such as arachnodactyly and visual or hearing impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Nephrotic syndrome 14
MedGen UID:
1617660
Concept ID:
C4540559
Disease or Syndrome
Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is characterized by varying combinations of steroid-resistant nephrotic syndrome (ranging from nonimmune fetal hydrops to adolescent onset), primary adrenal insufficiency (with or without mineralocorticoid deficiency), testicular insufficiency, hypothyroidism, ichthyosis, lymphopenia/immunodeficiency, and neurologic abnormalities that can include developmental delay, regression / progressive neurologic involvement, cranial nerve deficits, and peripheral motor and sensory neuropathy.
Focal segmental glomerulosclerosis 1
MedGen UID:
1636833
Concept ID:
C4551527
Disease or Syndrome
Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop the clinical entity called 'nephrotic syndrome' (see NPHS1; 256300), which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004; Mathis et al., 1998). D'Agati et al. (2011) provided a detailed review of FSGS, emphasizing that the disorder results from defects of the podocyte. Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Focal Segmental Glomerulosclerosis and Nephrotic Syndrome Focal segmental glomerulosclerosis and nephrotic syndrome are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also FSGS2 (603965), caused by mutation in the TRPC6 gene (603652); FSGS3 (607832), associated with variation in the CD2AP gene (604241); FSGS4 (612551), mapped to chromosome 22q12; FSGS5 (613237), caused by mutation in the INF2 gene (610982); FSGS6 (614131), caused by mutation in the MYO1E gene (601479); FSGS7 (616002), caused by mutation in the PAX2 gene (167409); FSGS8 (616032), caused by mutation in the ANLN gene (616027); FSGS9 (616220), caused by mutation in the CRB2 gene (609720); and FSGS10 (256020), caused by mutation in the LMX1B gene (602575). See also NPHS1 (256300), caused by mutation in the NPHS1 gene (602716); NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); NPHS4 (256370), caused by mutation in the WT1 gene (607102); NPHS5 (614199), caused by mutation in the LAMB2 gene (150325); NPHS6 (614196), caused by mutation in the PTPRO gene (600579); NPHS7 (615008), caused by mutation in the DGKE gene (601440); NPHS8 (615244), caused by mutation in the ARHGDIA gene (601925); NPHS9 (615573), caused by mutation in the COQ8B gene (615567); NPHS10 (615861), caused by mutation in the EMP2 gene (602334); NPHS11 (616730), caused by mutation in the NUP107 gene (607617); NPHS12 (616892), caused by mutation in the NUP93 gene (614351); NPHS13 (616893), caused by mutation in the NUP205 gene (614352); NPHS14 (617575), caused by mutation in the SGPL1 gene (603729); NPHS15 (617609), caused by mutation in the MAGI2 gene (606382); NPHS16 (617783), caused by mutation in the KANK2 gene (614610), NPHS17 (618176), caused by mutation in the NUP85 gene (170285); NPHS18 (618177), caused by mutation in the NUP133 gene (607613); NPHS19 (618178), caused by mutation in the NUP160 gene (607614); NPHS20 (301028), caused by mutation in the TBC1D8B gene (301027); and NPHS21 (618594) caused by mutation in the AVIL gene (613397).
Senior-Loken syndrome 1
MedGen UID:
1639722
Concept ID:
C4551559
Disease or Syndrome
Leber congenital amaurosis primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). Some people with Senior-Løken syndrome develop the signs of Leber congenital amaurosis within the first few years of life, while others do not develop vision problems until later in childhood.\n\nNephronophthisis causes fluid-filled cysts to develop in the kidneys beginning in childhood. These cysts impair kidney function, initially causing increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). Nephronophthisis leads to end-stage renal disease (ESRD) later in childhood or in adolescence. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.\n\nSenior-Løken syndrome is a rare disorder characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye condition known as Leber congenital amaurosis.
Renal hypomagnesemia 5 with ocular involvement
MedGen UID:
1648449
Concept ID:
C4721891
Disease or Syndrome
HOMG5 is an autosomal recessive disorder characterized by severe renal magnesium wasting, progressive renal failure, and nephrocalcinosis. Some patients also have severe visual impairment. Amelogenesis imperfecta has been reported in some patients (summary by Konrad et al., 2006 and Yamaguti et al., 2017). For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014.
Autosomal recessive Alport syndrome
MedGen UID:
1648334
Concept ID:
C4746745
Disease or Syndrome
In Alport syndrome (AS) a spectrum of phenotypes ranging from progressive renal disease with extrarenal abnormalities to isolated hematuria with a non-progressive or very slowly progressive course is observed. Approximately two thirds of AS is X-linked (XLAS); approximately 15% is autosomal recessive (ARAS), and approximately 20% is autosomal dominant (ADAS). In the absence of treatment, renal disease progresses from microscopic hematuria (microhematuria) to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with XLAS, and in all males and females with ARAS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with ADAS, ESRD is frequently delayed until later adulthood, SNHL is relatively late in onset, and ocular involvement is rare.
X-linked Alport syndrome
MedGen UID:
1648433
Concept ID:
C4746986
Disease or Syndrome
In Alport syndrome (AS) a spectrum of phenotypes ranging from progressive renal disease with extrarenal abnormalities to isolated hematuria with a non-progressive or very slowly progressive course is observed. Approximately two thirds of AS is X-linked (XLAS); approximately 15% is autosomal recessive (ARAS), and approximately 20% is autosomal dominant (ADAS). In the absence of treatment, renal disease progresses from microscopic hematuria (microhematuria) to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with XLAS, and in all males and females with ARAS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with ADAS, ESRD is frequently delayed until later adulthood, SNHL is relatively late in onset, and ocular involvement is rare.
Polycystic kidney disease 6 with or without polycystic liver disease
MedGen UID:
1648469
Concept ID:
C4748044
Disease or Syndrome
Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral kidney cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Kidney manifestations include early-onset hypertension, kidney pain, and kidney insufficiency. Approximately 50% of individuals with ADPKD have end-stage kidney disease (ESKD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD), most often in females. Overall, the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of kidney disease and other extra-kidney manifestations.
Nephrotic syndrome, type 17
MedGen UID:
1648294
Concept ID:
C4748545
Disease or Syndrome
NPHS17, a disease of the renal glomerular filter, is characterized by proteinuria, edema, and hypoalbuminemia. It does not respond to drug treatment and inevitably progresses to end-stage renal disease, thus requiring dialysis or renal transplantation for survival. Renal histology shows focal segmental glomerulosclerosis (Braun et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Nephrotic syndrome, type 18
MedGen UID:
1648464
Concept ID:
C4748549
Disease or Syndrome
NPHS18, a disease of the renal glomerular filter, is characterized by proteinuria, edema, and hypoalbuminemia. It does not respond to drug treatment and inevitably progresses to end-stage renal disease, thus requiring dialysis or renal transplantation for survival. Renal histology shows focal segmental glomerulosclerosis (Braun et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Mitochondrial complex 1 deficiency, nuclear type 29
MedGen UID:
1648451
Concept ID:
C4748830
Disease or Syndrome
Nephrotic syndrome, type 20
MedGen UID:
1678854
Concept ID:
C5193011
Disease or Syndrome
Nephrotic syndrome type 20 (NPHS20) is an X-linked renal disorder characterized by onset of steroid-resistant nephrotic syndrome and proteinuria in the first decade of life in affected males. The course of the disorder is highly variable: some patients progress to end-stage kidney disease and may die in childhood without renal transplantation, whereas others have milder symptoms and maintain normal renal function. Carrier females may have a milder disorder with proteinuria or may be unaffected. Renal biopsy typically shows focal segmental glomerulosclerosis (FSGS) and effacement of podocyte foot processes (summary by Dorval et al., 2019 and Kampf et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Galloway-Mowat syndrome 7
MedGen UID:
1679283
Concept ID:
C5193044
Disease or Syndrome
Galloway-Mowat syndrome-7 (GAMOS7) is an autosomal recessive disorder characterized by developmental delay, microcephaly, and early-onset nephrotic syndrome (summary by Rosti et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Galloway-Mowat syndrome 8
MedGen UID:
1675829
Concept ID:
C5193045
Disease or Syndrome
Galloway-Mowat syndrome-8 is an autosomal recessive disorder characterized by impaired psychomotor development, poor overall growth with microcephaly, and early-onset progressive nephrotic syndrome associated with focal segmental glomerulosclerosis on renal biopsy. Some patients may have seizures, and some may die in childhood (summary by Fujita et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Megabladder, congenital
MedGen UID:
1684806
Concept ID:
C5231472
Congenital Abnormality
Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females (Houweling et al., 2019).
Nephrotic syndrome, type 21
MedGen UID:
1684676
Concept ID:
C5231498
Disease or Syndrome
Nephrotic syndrome type 21 (NPHS21) is an autosomal recessive renal disorder characterized by onset of kidney dysfunction in the first year of life. Laboratory studies show proteinuria and renal biopsy shows diffuse mesangial sclerosis. The disorder is rapidly progressive and ultimately results in end-stage renal disease. Some patients with variable extrarenal manifestations, such as microcephaly or impaired intellectual development, have been reported, but it is not clear whether these features are consistently part of the phenotype (summary by Rao et al., 2017). (Rao et al. (2017) designated the disorder NPHS25.) For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Fanconi renotubular syndrome 5
MedGen UID:
1711127
Concept ID:
C5394473
Disease or Syndrome
Fanconi renotubular syndrome-5 (FRTS5) is a mitochondrial disorder characterized by proximal renotubular dysfunction from birth, followed by progressive kidney disease and pulmonary fibrosis. It occurs only in individuals of Acadian descent (Crocker et al., 1997 and Hartmannova et al., 2016). For a discussion of genetic heterogeneity of Fanconi renotubular syndrome, see FRTS1 (134600).
COACH syndrome 1
MedGen UID:
1769861
Concept ID:
C5435651
Disease or Syndrome
Any COACH syndrome in which the cause of the disease is a variation in the TMEM67 gene.
COACH syndrome 3
MedGen UID:
1755565
Concept ID:
C5436841
Disease or Syndrome
COACH syndrome is classically defined as Cerebellar vermis hypoplasia, Oligophrenia, Ataxia, Colobomas, and Hepatic fibrosis (Verloes and Lambotte, 1989). Brain MRI demonstrates the molar tooth sign, which is a feature of Joubert syndrome. The disorder has been described as a Joubert syndrome-related disorder with liver disease (summary by Doherty et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of COACH syndrome, see 216360.
Nephrotic syndrome, type 22
MedGen UID:
1745920
Concept ID:
C5436909
Disease or Syndrome
Nephrotic syndrome type 22 (NPHS22) is an autosomal recessive renal disease characterized by onset of progressive kidney dysfunction in infancy. Affected individuals usually present with edema associated with hypoproteinemia, proteinuria, and microscopic hematuria. Renal biopsy shows effacement of the podocyte foot processes, glomerulosclerosis, and thickening of the glomerular basement membrane. The disease is steroid-resistant and progressive, resulting in end-stage renal disease usually necessitating kidney transplant (Majmundar et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Nephronophthisis-like nephropathy 2
MedGen UID:
1794163
Concept ID:
C5561953
Disease or Syndrome
Nephronophthisis-like nephropathy-2 (NPHPL2) is an autosomal recessive cystic kidney disease characterized by onset of progressive renal insufficiency in the first decades of life. Renal imaging and biopsy show corticomedullary cysts, tubular ectasia, tubular basement membrane disruption, and tubulointerstitial infiltrations. Patients eventually progress to end-stage renal failure, necessitating kidney transplantation or dialysis (summary by Hurd et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100).
Aicardi-Goutieres syndrome 9
MedGen UID:
1794176
Concept ID:
C5561966
Disease or Syndrome
Aicardi-Goutieres syndrome-9 (AGS9) is a type I interferonopathy characterized by severe developmental delay and progressive neurologic deterioration. Patients present in infancy with irritability and spasticity. Brain imaging shows diffusely abnormal white matter, cerebral atrophy, and intracranial calcification. Premature death has been associated with renal and/or hepatic failure (Uggenti et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750).
Biliary, renal, neurologic, and skeletal syndrome
MedGen UID:
1794200
Concept ID:
C5561990
Disease or Syndrome
Biliary, renal, neurologic, and skeletal syndrome (BRENS) is an autosomal recessive complex ciliopathy with multisystemic manifestations. The most common presentation is severe neonatal cholestasis that progresses to liver fibrosis and cirrhosis. Most patients have additional clinical features suggestive of a ciliopathy, including postaxial polydactyly, hydrocephalus, retinal abnormalities, and situs inversus. Additional features of the syndrome may include congenital cardiac defects, echogenic kidneys with renal failure, ocular abnormalities, joint hyperextensibility, and dysmorphic facial features. Some patients have global developmental delay. Brain imaging typically shows dilated ventricles, hypomyelination, and white matter abnormalities, although some patients have been described with abnormal pituitary development (summary by Shaheen et al., 2020 and David et al., 2020).
Galloway-Mowat syndrome 9
MedGen UID:
1794226
Concept ID:
C5562016
Disease or Syndrome
Galloway-Mowat syndrome-9 (GAMOS9) is an autosomal recessive disorder characterized by onset of nephrotic syndrome with proteinuria in infancy or early childhood. The renal disease is slowly progressive, but some affected individuals may develop end-stage renal disease in the first decade. Renal biopsy shows focal segmental glomerulosclerosis (FSGS) or diffuse mesangial sclerosis (DMS). Affected individuals also have developmental delay and secondary microcephaly. Additional features may include facial dysmorphism and gastroesophageal reflux. Early death may occur (Arrondel et al., 2019). For a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Galloway-Mowat syndrome 10
MedGen UID:
1794230
Concept ID:
C5562020
Disease or Syndrome
Galloway-Mowat syndrome-10 (GAMOS10) is a severe autosomal recessive disorder characterized by onset of symptoms soon after birth. Affected individuals have progressive renal dysfunction with proteinuria associated with diffuse mesangial sclerosis (DMS) on renal biopsy. Other features include global developmental delay, microcephaly, hypothyroidism, arachnodactyly, and dysmorphic facial features. Some patients may have seizures or abnormalities on brain imaging. All reported patients have died in infancy (summary by Arrondel et al., 2019 and Schmidt et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Nephrotic syndrome, IIa 26
MedGen UID:
1823994
Concept ID:
C5774221
Disease or Syndrome
Nephrotic syndrome type 26 (NPHS26) is an autosomal recessive renal disorder characterized by onset of proteinuria in the first months or years of life. Other features may include edema and hypoalbuminemia. Renal biopsy shows focal segmental glomerulosclerosis (FSGS), diffuse mesangial sclerosis (DMS), abnormalities of the glomerular basement membrane, and effacement of podocyte foot processes. There is variability in disease progression and response to treatment: some patients respond to steroids, whereas others show steroid resistance and progression to end-stage renal disease (ESRD) (Braun et al., 2019; Taniguchi et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Polycystic kidney disease 7
MedGen UID:
1823995
Concept ID:
C5774222
Disease or Syndrome
Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral kidney cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Kidney manifestations include early-onset hypertension, kidney pain, and kidney insufficiency. Approximately 50% of individuals with ADPKD have end-stage kidney disease (ESKD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD), most often in females. Overall, the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of kidney disease and other extra-kidney manifestations.
Neurooculorenal syndrome
MedGen UID:
1841013
Concept ID:
C5830377
Disease or Syndrome
Neurooculorenal syndrome (NORS) is an autosomal recessive developmental disorder with highly variable clinical manifestations involving several organ systems. Some affected individuals present in utero with renal agenesis and structural brain abnormalities incompatible with life, whereas others present in infancy with a neurodevelopmental disorder characterized by global developmental delay and dysmorphic facial features that may be associated with congenital anomalies of the kidney and urinary tract (CAKUT). Additional more variable features may include ocular anomalies, most commonly strabismus, congenital heart defects, and pituitary hormone deficiency. Brain imaging usually shows structural midline defects, including dysgenesis of the corpus callosum and hindbrain. There is variation in the severity, manifestations, and expressivity of the phenotype, even within families (Rasmussen et al., 2018; Munch et al., 2022).
Autosomal dominant Alport syndrome
MedGen UID:
1848787
Concept ID:
C5882663
Disease or Syndrome
In Alport syndrome (AS) a spectrum of phenotypes ranging from progressive renal disease with extrarenal abnormalities to isolated hematuria with a non-progressive or very slowly progressive course is observed. Approximately two thirds of AS is X-linked (XLAS); approximately 15% is autosomal recessive (ARAS), and approximately 20% is autosomal dominant (ADAS). In the absence of treatment, renal disease progresses from microscopic hematuria (microhematuria) to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with XLAS, and in all males and females with ARAS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with ADAS, ESRD is frequently delayed until later adulthood, SNHL is relatively late in onset, and ocular involvement is rare.
Alport syndrome 3b, autosomal recessive
MedGen UID:
1848447
Concept ID:
C5882699
Disease or Syndrome
Autosomal recessive Alport syndrome-3B (ATS3B) is a progressive hematuric glomerulonephritis characterized by glomerular basement membrane abnormalities. Sensorineural hearing loss and ocular manifestations may be present (summary by Boye et al., 1998). For a general phenotypic description of Alport syndrome, see the X-linked dominant form (ATS1; 301050).

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PubMed

Agrawal U, Bedston S, McCowan C, Oke J, Patterson L, Robertson C, Akbari A, Azcoaga-Lorenzo A, Bradley DT, Fagbamigbe AF, Grange Z, Hall ECR, Joy M, Katikireddi SV, Kerr S, Ritchie L, Murphy S, Owen RK, Rudan I, Shah SA, Simpson CR, Torabi F, Tsang RSM, de Lusignan S, Lyons RA, O'Reilly D, Sheikh A
Lancet 2022 Oct 15;400(10360):1305-1320. doi: 10.1016/S0140-6736(22)01656-7. PMID: 36244382Free PMC Article
Zhang Y, Böckhaus J, Wang F, Wang S, Rubel D, Gross O, Ding J
Pediatr Nephrol 2021 Sep;36(9):2719-2730. Epub 2021 Mar 27 doi: 10.1007/s00467-021-05040-9. PMID: 33772369Free PMC Article
Nagler EV, Webster AC, Vanholder R, Zoccali C
Nephrol Dial Transplant 2012 Oct;27(10):3736-45. Epub 2012 Aug 1 doi: 10.1093/ndt/gfs295. PMID: 22859791

Recent clinical studies

Etiology

Yen FS, Hwu CM, Liu JS, Wu YL, Chong K, Hsu CC
Ann Intern Med 2024 Jun;177(6):693-700. Epub 2024 Apr 30 doi: 10.7326/M23-1874. PMID: 38684099
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Rivara MB, Mehrotra R
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Nagler EV, Webster AC, Vanholder R, Zoccali C
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Semin Dial 2012 Jan-Feb;25(1):50-8. Epub 2011 Oct 4 doi: 10.1111/j.1525-139X.2011.00986.x. PMID: 21967444

Diagnosis

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Therapy

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Prognosis

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Teruel JL, Burguera Vion V, Gomis Couto A, Rivera Gorrín M, Fernández-Lucas M, Rodríguez Mendiola N, Quereda C
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O'Connor NR, Kumar P
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Clinical prediction guides

Benz EG, Hartung EA
Pediatr Nephrol 2021 Sep;36(9):2639-2658. Epub 2021 Jan 21 doi: 10.1007/s00467-020-04869-w. PMID: 33474686Free PMC Article
Preka E, Shroff R, Stronach L, Calder F, Stefanidis CJ
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J Ayub Med Coll Abbottabad 2020 Apr-Jun;32(2):179-183. PMID: 32583990
Chen T, Lee VW, Harris DC
Med J Aust 2018 Sep 17;209(6):275-279. doi: 10.5694/mja18.00297. PMID: 30208820
Nagler EV, Webster AC, Vanholder R, Zoccali C
Nephrol Dial Transplant 2012 Oct;27(10):3736-45. Epub 2012 Aug 1 doi: 10.1093/ndt/gfs295. PMID: 22859791

Recent systematic reviews

de Lucena LA, Freitas MAA, Souza AKC, Silva CHA, Watanabe JMF, Guedes FL, Almeida JB, de Oliveira RA
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Fabrizi F, Cerutti R, Dixit V, Ridruejo E
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Hall RK, O'Hare AM, Anderson RA, Colón-Emeric CS
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O'Connor NR, Kumar P
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