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Renal-hepatic-pancreatic dysplasia 2(RHPD2)

MedGen UID:
815764
Concept ID:
C3809434
Disease or Syndrome
Synonym: RHPD2
 
Gene (location): NEK8 (17q11.2)
 
Monarch Initiative: MONDO:0014174
OMIM®: 615415

Definition

RHPD2 is an autosomal recessive multisystemic disorder with severe abnormalities apparent in utero and often resulting in fetal death or death in infancy. The main organs affected include the kidney, liver, and pancreas, although other abnormalities, including cardiac, skeletal, and lung defects, may also be present. Affected individuals often have situs inversus. The disorder results from a defect in ciliogenesis and ciliary function, as well as in cell proliferation and epithelial morphogenesis; thus, the clinical manifestations are highly variable (summary by Grampa et al., 2016). For a discussion of genetic heterogeneity of renal-hepatic-pancreatic dysplasia, see RHPD1 (208540). [from OMIM]

Clinical features

From HPO
Enlarged kidney
MedGen UID:
108156
Concept ID:
C0542518
Finding
An abnormal increase in the size of the kidney.
Cystic renal dysplasia
MedGen UID:
322533
Concept ID:
C1834931
Congenital Abnormality
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Truncus arteriosus
MedGen UID:
22501
Concept ID:
C0041206
Embryonic Structure
A single arterial trunk arises from the cardiac mass. The pulmonary arteries, aorta and coronary arteries arise from this single trunk with no evidence of another outflow tract.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Situs inversus
MedGen UID:
1642262
Concept ID:
C4551493
Congenital Abnormality
A left-right reversal (or "mirror reflection") of the anatomical location of the major thoracic and abdominal organs.
Cholestasis
MedGen UID:
925
Concept ID:
C0008370
Disease or Syndrome
Impairment of bile flow due to obstruction in bile ducts.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Hepatic cysts
MedGen UID:
82761
Concept ID:
C0267834
Disease or Syndrome
A cystic lesion located in the liver.
Malformation of the hepatic ductal plate
MedGen UID:
346605
Concept ID:
C1857519
Finding
Enlarged cisterna magna
MedGen UID:
344031
Concept ID:
C1853377
Finding
Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Abnormal lung lobation
MedGen UID:
195782
Concept ID:
C0685695
Congenital Abnormality
A developmental defect in the formation of pulmonary lobes.
Asplenia
MedGen UID:
108652
Concept ID:
C0600031
Congenital Abnormality
Absence (aplasia) of the spleen.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.

Recent clinical studies

Etiology

Frank V, Habbig S, Bartram MP, Eisenberger T, Veenstra-Knol HE, Decker C, Boorsma RA, Göbel H, Nürnberg G, Griessmann A, Franke M, Borgal L, Kohli P, Völker LA, Dötsch J, Nürnberg P, Benzing T, Bolz HJ, Johnson C, Gerkes EH, Schermer B, Bergmann C
Hum Mol Genet 2013 Jun 1;22(11):2177-85. Epub 2013 Feb 14 doi: 10.1093/hmg/ddt070. PMID: 23418306
Bernstein J, Chandra M, Creswell J, Kahn E, Malouf NN, McVicar M, Weinberg AG, Wybel RE
Am J Med Genet 1987 Feb;26(2):391-403. doi: 10.1002/ajmg.1320260218. PMID: 3812591

Diagnosis

Inaguma Y, Kaito H, Morisada N, Iijima K, Tanaka R
Pediatr Int 2019 Feb;61(2):210-212. Epub 2019 Feb 7 doi: 10.1111/ped.13758. PMID: 30734414
Rajagopalan R, Grochowski CM, Gilbert MA, Falsey AM, Coleman K, Romero R, Loomes KM, Piccoli DA, Devoto M, Spinner NB
Am J Med Genet A 2016 Mar;170(3):750-3. Epub 2015 Dec 24 doi: 10.1002/ajmg.a.37512. PMID: 26697755
Bendon RW
Pediatr Dev Pathol 1999 Jan-Feb;2(1):94-100. doi: 10.1007/s100249900096. PMID: 9841713
Devriendt K, Dooms L, Proesmans W, de Zegher F, Desmet V, Eggermont E
Eur J Pediatr 1996 Feb;155(2):87-90. doi: 10.1007/BF02075756. PMID: 8775219
Bernstein J, Chandra M, Creswell J, Kahn E, Malouf NN, McVicar M, Weinberg AG, Wybel RE
Am J Med Genet 1987 Feb;26(2):391-403. doi: 10.1002/ajmg.1320260218. PMID: 3812591

Prognosis

Gunther K, Imseis EM, Samuel JP, Hillman EA, Ojala TH, Jahnukainen T, Hillman PR
Mol Genet Genomic Med 2023 Apr;11(4):e2135. Epub 2023 Feb 8 doi: 10.1002/mgg3.2135. PMID: 36756677Free PMC Article

Clinical prediction guides

Rajagopalan R, Grochowski CM, Gilbert MA, Falsey AM, Coleman K, Romero R, Loomes KM, Piccoli DA, Devoto M, Spinner NB
Am J Med Genet A 2016 Mar;170(3):750-3. Epub 2015 Dec 24 doi: 10.1002/ajmg.a.37512. PMID: 26697755
Frank V, Habbig S, Bartram MP, Eisenberger T, Veenstra-Knol HE, Decker C, Boorsma RA, Göbel H, Nürnberg G, Griessmann A, Franke M, Borgal L, Kohli P, Völker LA, Dötsch J, Nürnberg P, Benzing T, Bolz HJ, Johnson C, Gerkes EH, Schermer B, Bergmann C
Hum Mol Genet 2013 Jun 1;22(11):2177-85. Epub 2013 Feb 14 doi: 10.1093/hmg/ddt070. PMID: 23418306
Devriendt K, Dooms L, Proesmans W, de Zegher F, Desmet V, Eggermont E
Eur J Pediatr 1996 Feb;155(2):87-90. doi: 10.1007/BF02075756. PMID: 8775219