title: Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families.
abstract: BACKGROUND
  Asphyxiating Thoracic Dysplasia (ATD) belongs to the short rib polydactyly group and is characterized by a narrow thorax, short long bones and trident acetabular roof. Other reported features include polydactyly, renal, liver and retinal involvement. To date, mutations in IFT80, DYNC2H1, TTC21B and WDR19 have been reported in ATD. The clinical and molecular heterogeneity leads to difficulties in the evaluation of the long-term prognosis.
  
  
  METHODS
  We investigated 53 ATD cases (23 living cases and 30 fetuses) from 39 families. They benefited from a combined approach of deep phenotyping and IFT80 and DYNC2H1 molecular screening.
  
  
  RESULTS
  Among the 23 postnatal cases, pulmonary insufficiency was noted in 60% of cases, with tracheotomy requirement in five cases. Renal and liver diseases occurred respectively in 17% and 22% of cases, whereas retinal alteration was present in 50% of cases aged more than 5 years. We identified DYNC2H1 mutations in 23 families (59%) and IFT80 mutations in two families (5%). However, in six families, only one heterozygote mutation in either IFT80 or DYNC2H1 was identified. Finally, the two genes were excluded in 14 families (36%).
  
  
  CONCLUSIONS
  We conclude that DYNC2H1 is a major gene responsible for ATD, while IFT80 is rarely involved. The presence of only one mutation in six families and the exclusion of the two genes in 14 families support the involvement of other causal cilia genes. The long-term follow up emphasizes that the pulmonary prognosis is probably less pejorative and retinal involvement more frequent than previously thought.
authors: Département de Génétique et INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Fondation Imagine, Hôpital Necker-Enfants malades, AP-HP, Paris, France.
authors: Geneviève
authors: G
authors: Baujat
authors: Céline
authors: C
authors: Huber
authors: Joyce
authors: J
authors: El Hokayem
authors: Roseline
authors: R
authors: Caumes
authors: Claire
authors: C
authors: Do Ngoc Thanh
authors: Albert
authors: A
authors: David
authors: Anne-Lise
authors: AL
authors: Delezoide
authors: Anne
authors: A
authors: Dieux-Coeslier
authors: Brigitte
authors: B
authors: Estournet
authors: Christine
authors: C
authors: Francannet
authors: Honorine
authors: H
authors: Kayirangwa
authors: Florence
authors: F
authors: Lacaille
authors: Muriel
authors: M
authors: Le Bourgeois
authors: Jelena
authors: J
authors: Martinovic
authors: Rémi
authors: R
authors: Salomon
authors: Sabine
authors: S
authors: Sigaudy
authors: Valérie
authors: V
authors: Malan
authors: Arnold
authors: A
authors: Munnich
authors: Martine
authors: M
authors: Le Merrer
authors: Kim Hanh
authors: KH
authors: Le Quan Sang
authors: Valérie
authors: V
authors: Cormier-Daire
mesh_terms: D000028:Abortion, Induced; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D056445:Cytoplasmic Dyneins / Q000235:genetics; D004613:Ellis-Van Creveld Syndrome / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D005333:Fetus / Q000002:abnormalities; D005602:France; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016216:Ultrasonography, Prenatal
chemical_list: C099883:DYNC2H1 protein, human; D056445:Cytoplasmic Dyneins