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Asphyxiating thoracic dystrophy 5(SRTD5)

MedGen UID:
482228
Concept ID:
C3280598
Disease or Syndrome
Synonyms: SHORT-RIB THORACIC DYSPLASIA 5 WITH OR WITHOUT POLYDACTYLY; SHORT-RIB THORACIC DYSPLASIA 5 WITHOUT POLYDACTYLY; SRTD5
 
Gene (location): WDR19 (4p14)
 
Monarch Initiative: MONDO:0013717
OMIM®: 614376

Definition

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). [from OMIM]

Additional description

From MedlinePlus Genetics
Some people with asphyxiating thoracic dystrophy are born with less severe skeletal abnormalities and have only mild breathing difficulties, such as rapid breathing or shortness of breath. These individuals may live into adolescence or adulthood. After infancy, people with this condition may develop life-threatening kidney (renal) abnormalities that cause the kidneys to malfunction or fail. Heart defects and a narrowing of the airway (subglottic stenosis) are also possible. Other, less common features of asphyxiating thoracic dystrophy include liver disease, fluid-filled sacs (cysts) in the pancreas, dental abnormalities, and an eye disease called retinal dystrophy that can lead to vision loss.

Asphyxiating thoracic dystrophy, also known as Jeune syndrome, is an inherited disorder of bone growth characterized by a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (polydactyly). Additional skeletal abnormalities can include unusually shaped collarbones (clavicles) and pelvic bones, and and cone-shaped ends of the long bones in the arms and legs. Many infants with this condition are born with an extremely narrow, bell-shaped chest that can restrict the growth and expansion of the lungs. Life-threatening problems with breathing result, and people with asphyxiating thoracic dystrophy may live only into infancy or early childhood. However, in people who survive beyond the first few years, the narrow chest and related breathing problems can improve with age.  https://medlineplus.gov/genetics/condition/asphyxiating-thoracic-dystrophy

Clinical features

From HPO
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Chronic tubulointerstitial nephritis
MedGen UID:
65957
Concept ID:
C0238304
Disease or Syndrome
Chronic inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
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.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Pes valgus
MedGen UID:
299028
Concept ID:
C1578482
Anatomical Abnormality
An outward deviation of the foot at the talocalcaneal or subtalar joint.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Acetabular spurs
MedGen UID:
814600
Concept ID:
C3808270
Finding
The presence of osteophytes (bone spurs), i.e., of bony projections originating from the acetabulum.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Thoracic dysplasia
MedGen UID:
853272
Concept ID:
C1406921
Congenital Abnormality
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Short iliac bones
MedGen UID:
336488
Concept ID:
C1849063
Finding
Underdevelopment of the iliac bones.
Broad long bone diaphyses
MedGen UID:
870604
Concept ID:
C4025053
Anatomical Abnormality
Increased width of the diaphysis of long bones.
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Glomerulonephritis
MedGen UID:
6616
Concept ID:
C0017658
Disease or Syndrome
Inflammation of the renal glomeruli.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Supernumerary nipple
MedGen UID:
120564
Concept ID:
C0266011
Congenital Abnormality
Presence of more than two nipples.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Attenuation of retinal blood vessels
MedGen UID:
480605
Concept ID:
C3278975
Finding

Term Hierarchy

Recent clinical studies

Etiology

Muthialu N, Mussa S, Owens CM, Bulstrode N, Elliott MJ
Eur J Cardiothorac Surg 2014 Oct;46(4):643-7. Epub 2014 Mar 5 doi: 10.1093/ejcts/ezu074. PMID: 24599166
Poyner SE, Bradshaw WT
Neonatal Netw 2013 Sep-Oct;32(5):342-52. doi: 10.1891/0730-0832.32.5.342. PMID: 23985472
Baujat G, Huber C, El Hokayem J, Caumes R, Do Ngoc Thanh C, David A, Delezoide AL, Dieux-Coeslier A, Estournet B, Francannet C, Kayirangwa H, Lacaille F, Le Bourgeois M, Martinovic J, Salomon R, Sigaudy S, Malan V, Munnich A, Le Merrer M, Le Quan Sang KH, Cormier-Daire V
J Med Genet 2013 Feb;50(2):91-8. doi: 10.1136/jmedgenet-2012-101282. PMID: 23339108
Schaballie H, Renard M, Vermylen C, Scheers I, Revencu N, Regal L, Cassiman D, Sevenants L, Hoffman I, Corveleyn A, Bordon V, Haerynck F, Allegaert K, De Boeck K, Roskams T, Boeckx N, Bossuyt X, Meyts I
Eur J Pediatr 2013 May;172(5):613-22. Epub 2013 Jan 12 doi: 10.1007/s00431-012-1908-0. PMID: 23315050
Dagoneau N, Goulet M, Geneviève D, Sznajer Y, Martinovic J, Smithson S, Huber C, Baujat G, Flori E, Tecco L, Cavalcanti D, Delezoide AL, Serre V, Le Merrer M, Munnich A, Cormier-Daire V
Am J Hum Genet 2009 May;84(5):706-11. doi: 10.1016/j.ajhg.2009.04.016. PMID: 19442771Free PMC Article

Diagnosis

Gilligan LA, Calvo-Garcia MA, Weaver KN, Kline-Fath BM
Pediatr Radiol 2020 Feb;50(2):224-233. Epub 2019 Nov 27 doi: 10.1007/s00247-019-04537-8. PMID: 31776601
Poyner SE, Bradshaw WT
Neonatal Netw 2013 Sep-Oct;32(5):342-52. doi: 10.1891/0730-0832.32.5.342. PMID: 23985472
Baujat G, Huber C, El Hokayem J, Caumes R, Do Ngoc Thanh C, David A, Delezoide AL, Dieux-Coeslier A, Estournet B, Francannet C, Kayirangwa H, Lacaille F, Le Bourgeois M, Martinovic J, Salomon R, Sigaudy S, Malan V, Munnich A, Le Merrer M, Le Quan Sang KH, Cormier-Daire V
J Med Genet 2013 Feb;50(2):91-8. doi: 10.1136/jmedgenet-2012-101282. PMID: 23339108
Schaballie H, Renard M, Vermylen C, Scheers I, Revencu N, Regal L, Cassiman D, Sevenants L, Hoffman I, Corveleyn A, Bordon V, Haerynck F, Allegaert K, De Boeck K, Roskams T, Boeckx N, Bossuyt X, Meyts I
Eur J Pediatr 2013 May;172(5):613-22. Epub 2013 Jan 12 doi: 10.1007/s00431-012-1908-0. PMID: 23315050
Dagoneau N, Goulet M, Geneviève D, Sznajer Y, Martinovic J, Smithson S, Huber C, Baujat G, Flori E, Tecco L, Cavalcanti D, Delezoide AL, Serre V, Le Merrer M, Munnich A, Cormier-Daire V
Am J Hum Genet 2009 May;84(5):706-11. doi: 10.1016/j.ajhg.2009.04.016. PMID: 19442771Free PMC Article

Therapy

O'Brien A, Roth MK, Athreya H, Reinker K, Koeck W, Patil V, Trevino H, Simmons J, Joshi AP, Smith MD, Campbell RM
J Pediatr Orthop 2015 Dec;35(8):783-97. doi: 10.1097/BPO.0000000000000383. PMID: 25575358
Abola RE, Tan J, Wallach D, Kier C, Seidman PA, Tobias JD
Middle East J Anaesthesiol 2010 Jun;20(5):735-8. PMID: 20803866

Prognosis

Gilligan LA, Calvo-Garcia MA, Weaver KN, Kline-Fath BM
Pediatr Radiol 2020 Feb;50(2):224-233. Epub 2019 Nov 27 doi: 10.1007/s00247-019-04537-8. PMID: 31776601
Poyner SE, Bradshaw WT
Neonatal Netw 2013 Sep-Oct;32(5):342-52. doi: 10.1891/0730-0832.32.5.342. PMID: 23985472
Schmidts M, Arts HH, Bongers EM, Yap Z, Oud MM, Antony D, Duijkers L, Emes RD, Stalker J, Yntema JB, Plagnol V, Hoischen A, Gilissen C, Forsythe E, Lausch E, Veltman JA, Roeleveld N, Superti-Furga A, Kutkowska-Kazmierczak A, Kamsteeg EJ, Elçioğlu N, van Maarle MC, Graul-Neumann LM, Devriendt K, Smithson SF, Wellesley D, Verbeek NE, Hennekam RC, Kayserili H, Scambler PJ, Beales PL; UK10K, Knoers NV, Roepman R, Mitchison HM
J Med Genet 2013 May;50(5):309-23. Epub 2013 Mar 1 doi: 10.1136/jmedgenet-2012-101284. PMID: 23456818Free PMC Article
Baujat G, Huber C, El Hokayem J, Caumes R, Do Ngoc Thanh C, David A, Delezoide AL, Dieux-Coeslier A, Estournet B, Francannet C, Kayirangwa H, Lacaille F, Le Bourgeois M, Martinovic J, Salomon R, Sigaudy S, Malan V, Munnich A, Le Merrer M, Le Quan Sang KH, Cormier-Daire V
J Med Genet 2013 Feb;50(2):91-8. doi: 10.1136/jmedgenet-2012-101282. PMID: 23339108
Keppler-Noreuil KM, Adam MP, Welch J, Muilenburg A, Willing MC
Am J Med Genet A 2011 May;155A(5):1021-32. Epub 2011 Apr 4 doi: 10.1002/ajmg.a.33892. PMID: 21465651

Clinical prediction guides

Stembalska A, Rydzanicz M, Klaniewska M, Dudarewicz L, Pollak A, Biela M, Stawinski P, Ploski R, Smigiel R
Genes (Basel) 2022 Jul 27;13(8) doi: 10.3390/genes13081339. PMID: 35893076Free PMC Article
Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Shaheen R, Schmidts M, Faqeih E, Hashem A, Lausch E, Holder I, Superti-Furga A; UK10K Consortium, Mitchison HM, Almoisheer A, Alamro R, Alshiddi T, Alzahrani F, Beales PL, Alkuraya FS
Hum Mol Genet 2015 Mar 1;24(5):1410-9. Epub 2014 Oct 30 doi: 10.1093/hmg/ddu555. PMID: 25361962Free PMC Article
Schaballie H, Renard M, Vermylen C, Scheers I, Revencu N, Regal L, Cassiman D, Sevenants L, Hoffman I, Corveleyn A, Bordon V, Haerynck F, Allegaert K, De Boeck K, Roskams T, Boeckx N, Bossuyt X, Meyts I
Eur J Pediatr 2013 May;172(5):613-22. Epub 2013 Jan 12 doi: 10.1007/s00431-012-1908-0. PMID: 23315050
Keppler-Noreuil KM, Adam MP, Welch J, Muilenburg A, Willing MC
Am J Med Genet A 2011 May;155A(5):1021-32. Epub 2011 Apr 4 doi: 10.1002/ajmg.a.33892. PMID: 21465651

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