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Asphyxiating thoracic dystrophy 4(SRTD4)

MedGen UID:
462535
Concept ID:
C3151185
Disease or Syndrome
Synonyms: SHORT-RIB THORACIC DYSPLASIA 4; SHORT-RIB THORACIC DYSPLASIA 4 WITH OR WITHOUT POLYDACTYLY; SRTD4
 
Gene (location): TTC21B (2q24.3)
 
Monarch Initiative: MONDO:0013441
OMIM®: 613819

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
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.

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.  https://medlineplus.gov/genetics/condition/asphyxiating-thoracic-dystrophy

Clinical features

From HPO
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.
Polydactyly
MedGen UID:
57774
Concept ID:
C0152427
Congenital Abnormality
A congenital anomaly characterized by the presence of supernumerary fingers or toes.
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.
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).
Hepatic cysts
MedGen UID:
82761
Concept ID:
C0267834
Disease or Syndrome
A cystic lesion located in the liver.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.

Term Hierarchy

Recent clinical studies

Etiology

Ijaz A, Alfadhli F, Alharbi A, Khan YN, Alhawas YK, Hashmi JA, Wali A, Basit S
Eur J Med Genet 2022 Oct;65(10):104578. Epub 2022 Aug 17 doi: 10.1016/j.ejmg.2022.104578. PMID: 35987473
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
Dumitrescu AV, Pfeifer WL, Drack AV
J AAPOS 2021 Aug;25(4):220.e1-220.e8. Epub 2021 Jul 17 doi: 10.1016/j.jaapos.2021.03.015. PMID: 34280564
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF; UK10K Consortium; University of Washington Center for Mendelian Genomics, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA
Nat Cell Biol 2015 Aug;17(8):1074-1087. Epub 2015 Jul 13 doi: 10.1038/ncb3201. PMID: 26167768Free PMC Article
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

Diagnosis

Piceci-Sparascio F, Micale L, Torres B, Guida V, Consoli F, Torrente I, Onori A, Frustaci E, D'Asdia MC, Petrizzelli F, Bernardini L, Mancini C, Soli F, Cocciadiferro D, Guadagnolo D, Mastromoro G, Putotto C, Fontana F, Brunetti-Pierri N, Novelli A, Pizzuti A, Marino B, Digilio MC, Mazza T, Dallapiccola B, Ruiz-Perez VL, Tartaglia M, Castori M, De Luca A
Eur J Hum Genet 2023 Apr;31(4):479-484. Epub 2023 Jan 4 doi: 10.1038/s41431-022-01276-7. PMID: 36599940Free PMC Article
Ijaz A, Alfadhli F, Alharbi A, Khan YN, Alhawas YK, Hashmi JA, Wali A, Basit S
Eur J Med Genet 2022 Oct;65(10):104578. Epub 2022 Aug 17 doi: 10.1016/j.ejmg.2022.104578. PMID: 35987473
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
Dumitrescu AV, Pfeifer WL, Drack AV
J AAPOS 2021 Aug;25(4):220.e1-220.e8. Epub 2021 Jul 17 doi: 10.1016/j.jaapos.2021.03.015. PMID: 34280564
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
Sacco Casamassima MG, Goldstein SD, Salazar JH, Papandria D, McIltrot KH, O'Neill DE, Abdullah F, Colombani PM
J Pediatr Surg 2014 Jan;49(1):55-60; discussion 60. Epub 2013 Oct 5 doi: 10.1016/j.jpedsurg.2013.09.027. PMID: 24439581
Betz RR, Mulcahey MJ, Ramirez N, Flynn JM, Smith JT, St Hilaire T, Campbell RM
J Pediatr Orthop 2008 Dec;28(8):850-3. doi: 10.1097/BPO.0b013e31818e19a4. PMID: 19034177
Weber TR
J Pediatr Surg 2005 Jan;40(1):170-3. doi: 10.1016/j.jpedsurg.2004.09.039. PMID: 15868580
Nakagawa M, Kise K, Okamoto N, Fujino H, Iwai M, Nomura Y, Sawa H
Clin Nephrol 2005 Apr;63(4):313-6. doi: 10.5414/cnp63313. PMID: 15847261

Prognosis

Vig A, Poulter JA, Ottaviani D, Tavares E, Toropova K, Tracewska AM, Mollica A, Kang J, Kehelwathugoda O, Paton T, Maynes JT, Wheway G, Arno G; Genomics England Research Consortium, Khan KN, McKibbin M, Toomes C, Ali M, Di Scipio M, Li S, Ellingford J, Black G, Webster A, Rydzanicz M, Stawiński P, Płoski R, Vincent A, Cheetham ME, Inglehearn CF, Roberts A, Heon E
Genet Med 2020 Dec;22(12):2041-2051. Epub 2020 Aug 5 doi: 10.1038/s41436-020-0915-1. PMID: 32753734Free PMC Article
Čechová A, Baxová A, Zeman J, Lambert L, Honzík T, Leiská A, Čunát V, Tesařová M
Prague Med Rep 2019;120(4):124-130. doi: 10.14712/23362936.2019.17. PMID: 31935347
Andrade CF, Cardoso PF, Felicetti JC
Thorac Cardiovasc Surg 2011 Feb;59(1):56-8. Epub 2011 Jan 17 doi: 10.1055/s-2008-1038987. PMID: 21243577
Gadepalli SK, Hirschl RB, Tsai WC, Caird MS, Vanderhave KL, Strouse PJ, Drongowski RA, Farley FA
J Pediatr Surg 2011 Jan;46(1):77-80. doi: 10.1016/j.jpedsurg.2010.09.070. PMID: 21238644
Potocki L, Abuelo DN, Oyer CE
Am J Med Genet 1995 Nov 20;59(3):295-9. doi: 10.1002/ajmg.1320590306. PMID: 8599352

Clinical prediction guides

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
Vig A, Poulter JA, Ottaviani D, Tavares E, Toropova K, Tracewska AM, Mollica A, Kang J, Kehelwathugoda O, Paton T, Maynes JT, Wheway G, Arno G; Genomics England Research Consortium, Khan KN, McKibbin M, Toomes C, Ali M, Di Scipio M, Li S, Ellingford J, Black G, Webster A, Rydzanicz M, Stawiński P, Płoski R, Vincent A, Cheetham ME, Inglehearn CF, Roberts A, Heon E
Genet Med 2020 Dec;22(12):2041-2051. Epub 2020 Aug 5 doi: 10.1038/s41436-020-0915-1. PMID: 32753734Free PMC Article
Čechová A, Baxová A, Zeman J, Lambert L, Honzík T, Leiská A, Čunát V, Tesařová M
Prague Med Rep 2019;120(4):124-130. doi: 10.14712/23362936.2019.17. PMID: 31935347
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF; UK10K Consortium; University of Washington Center for Mendelian Genomics, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA
Nat Cell Biol 2015 Aug;17(8):1074-1087. Epub 2015 Jul 13 doi: 10.1038/ncb3201. PMID: 26167768Free PMC Article
Sacco Casamassima MG, Goldstein SD, Salazar JH, Papandria D, McIltrot KH, O'Neill DE, Abdullah F, Colombani PM
J Pediatr Surg 2014 Jan;49(1):55-60; discussion 60. Epub 2013 Oct 5 doi: 10.1016/j.jpedsurg.2013.09.027. PMID: 24439581

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