Asphyxiating thoracic dysplasia is a rare autosomal recessive chondrodysplasia with multiorgan involvement.
It ofen leads to death in infancy because of a severely constricted thoracic cage and respiratory insufficiency. ATD1 is located at 15q13 (MIM.208500) and ATD2 at 3q24-q26 (mutations in the IFT80 gene on 3q) (MIM.611263).
Autosomal recessive disease. Frequency 1/100,000 - 1/130,000 live births
Synopsis
systemic anomalies
- short stature
- death in infancy secondary to pulmonary insufficiency
- survivors may develop renal insufficiency and hepatic dysfunction
retinal anomalies
craniofacial anomalies
- lingual papillomas (rare) (8723090)
- lobulation of the tongue (rare) (8723090)
- notches of the alveolar ridges (rare) (8723090)
thoracic anomalies
- narrow thorax
- pulmonary hypoplasia
- recurrent respiratory infections
hepatic anomalies (12800072)
- liver fibrocystic disease (LFCD)
- hepatic fibrosis
- bile duct proliferation
- polycystic liver disease
- jaundice
- biliary cirrhosis
pancreatic anomalies
renal anomalies
- chronic nephritis
- chronic renal failure
- bilateral non-obstructive multicystic renal dysplasia (BNOMRD)
- renal impairment
- renal cystic changes
- periglomerular fibrosis (12807964)
hypospadias (rare) (8723090)
postaxial polydactyly (rare) (8723090)
preaxial polydactyly (rare) (8723090)
skeletal anomalies
- long thorax
- narrow thorax
- short ribs
- horizontal ribs
- bulbous ribs
- irregular rib ends
- handlebar clavicles
- lacunar skull
- dysplastic pelvis (pelvic dysplasia)
- small pelvis
- hypoplastic iliac wings (infancy)
- rident acetabular roofs
- early ossification of capital femoral epiphyses (infancy)
- sciatic notch spur
- irregular metaphyses (childhood)
- irregular epiphyses (childhood)
- relatively short ulnae (childhood)
- short long bones
- relatively short fibulae (childhood)
- cone-shaped epiphyses (childhood)
- hand and foot polydactyly
- short phalanges
- acromelic shortening
- short limbs
- bowed long tubular bones (mesomelic campomelia) (8723090)
cutaneous anomalies
cerebral anomalies
- internal hydrocephalus (rare) (8723090)
- absence of corpus callosum (rare) (8723090)
Associations
short-rib polydactyly type 3 (SPS3) (Verma-Naumoff type) (familial association) (10710229)
Differential diagnosis
short-rib polydactyly type III (Verma-Naumoff) (10710229)
Ellis-van Creveld syndrome
renohepatopancreatic dysplastic syndromes (renal-hepatic-pancreatic dysplasias) (2325105, 3812591)
Etiology
Locus ATD1: located at 15q13 (MIM.208500) (12807964)
Locus ATD2: germline mutations in the IFT80 gene on 3q24-q26 (MIM.611263) (17468754)
References
Beales PL, Bland E, Tobin JL, Bacchelli C, Tuysuz B, Hill J, Rix S, Pearson CG, Kai M, Hartley J, Johnson C, Irving M, Elcioglu N, Winey M, Tada M, Scambler PJ.IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy.Nat Genet. 2007 Jun;39(6):727-9. Epub 2007 Apr 29. PMID: 17468754
Ho NC, Francomano CA, van Allen M. Jeune asphyxiating thoracic dystrophy and short-rib polydactyly type III (Verma-Naumoff) are variants of the same disorder. Am J Med Genet. 2000 Feb 14;90(4):310-4. PMID: 10710229
Majewski E, Oztürk B, Gillessen-Kaesbach G.Jeune syndrome with tongue lobulation and preaxial polydactyly, and Jeune syndrome with situs inversus and asplenia: compound heterozygosity Jeune-Mohr and Jeune-Ivemark?Am J Med Genet. 1996 May 3;63(1):74-9. PMID: 8723090 [PubMed - indexed for MEDLINE]
Yang SS, Langer LO Jr, Cacciarelli A, Dahms BB, Unger ER, Roskamp J, Dinno ND, Chen H.Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrome spectrum: a clinicopathologic study.Am J Med Genet Suppl. 1987;3:191-207. PMID: 3130854