Asphyxiating Thoracic Dystrophy (Jeune Syndrome) Clinical Presentation

Updated: May 01, 2019
  • Author: Santina A Zanelli, MD; Chief Editor: Maria Descartes, MD  more...
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Clinical presentations of lethal, severe, and latent forms of JS vary.

  • Respiratory distress: Respiratory distress may occur secondary to a small thorax. The thorax remains motionless, and respiration is entirely abdominal. Considerable supraclavicular and suprasternal retraction of the intercostal space may be present upon inspiration. Severe dyspnea and extreme cyanosis may occur. However, some infants have only respiratory symptoms in conjunction with infection. Some individuals with JS have no respiratory symptoms in infancy or childhood.

  • Chest deformity of varying degree

  • Variable limb shortening

  • Other symptoms: History may also reveal failure to thrive, gastroenteritis, recurrent rectal prolapse, diarrhea, congestive cardiac failure, puffy face, and ankle swelling.




Characteristics include the following:

  • Narrowed thorax (bell shaped or long and narrow) with reduced thoracic cage capacity; lung hypoplasia - The bell-shaped thorax is usually associated with early respiratory failure, while patients with a long and narrow chest may have mild respiratory symptoms
  • Shortened ribs with horizontal alignment

  • Dysplastic costochondral junctions

  • The small thorax usually improves with age for those who survive early childhood


Characteristics include the following:

  • Variable limb shortening
  • Brachydactyly
  • Occasional postaxial polydactyly of the hands and feet


Characteristics include the following

  • 40% of patients with JS develop renal complications
  • Renal failure due to nephron ciliary defect may develop during infancy, early adolescence, or the second decade of life
  • An inability to concentrate urine is the earliest manifestation
  • Polyuria, polydipsia, and hypertension may be present during the second or third year of life


Characteristics include the following:

  • Optic nerve hypoplasia
  • Retinal dystrophy

  • Abnormal retinal pigmentation

Hepatic and gastrointestinal

Characteristics include the following:

  • Liver involvement (30% of cases) may lead to prolonged neonatal jaundice, polycystic liver disease, hyperplasia of the bile ducts, and congenital hepatic cirrhosis; signs may include vomiting, hyperbilirubinemia, elevated transaminases, hepatomegaly, and portal hypertension [5]
  • Cystic changes of the pancreatic ducts and pancreatic exocrine insufficiency may be present in long-term survivors of JS
  • Hirschsprung disease


Occasional involvement of the heart may include cardiac failure secondary to increased pulmonary vascular resistance, thoracic constriction, alveolar hypoplasia, and possible intrinsic myocardial disease.


Occasional involvement of the teeth, nails, and other organs may occur.



JS is known to be genetically heterogeneous and is the first chondrodysplasia to be linked to a defect in intraflagellar transport (IFT) or primary cilia function.

JS is a member of the family of skeletal ciliopathies, disorders associated with dysfunction of primary cilia, classified as 1 of the 6 short-rib polydactyly syndrome (SRPS) disorders. [6]  JS, along with Ellis–van Creveld syndrome, is an SRPS compatible with life, rather than 1 of the 4 lethal SRPS subtypes (SRPS I–IV). [7] In addition, JS is both phenotypically and genetically related to Sensenbrenner syndrome (cranioectodermal dysplasia; MIM 218330) [8] and Mainzer-Saldino syndrome (conorenal syndrome; MIM 266920). [9]

Genetic mutations have been mapped to several loci: 4p14, 2q24.3, 15q13,3q24-3q26, and 11q14.3-q23.1.

Currently identified gene mutations include the following:

  • IFT80 [10]
  • TTC21B/ IFT139 [11]
  • TCTEX1D2 [12]
  • IFT140 [9, 13]
  • WDR19/ IFT144 8
  • WDR35 [14]
  • WDR60 [15, 16]
  • DYNC2H1, [17] most common

All of these genes encode for proteins that participate in ciliary IFT, an evolutionarily conserved process that is essential for ciliogenesis and governs a variety of important cell-signaling events key to normal human development. [18, 19]

Schmidts et al detected 34 DYNC2H1 mutations in 29 (41%) of 71 patients from 19 (33%) of 57 families, showing it as a major cause of asphyxiating thoracic dystrophy, especially in Northern European patients. [13]  This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site), but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. DYNC2H1 patients largely lacked significant extraskeletal involvement, demonstrating an important genotype–phenotype correlation

Significant variability exists in the course and severity of the thoracic phenotype both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles. This suggests that the DYNC2H1 phenotype may be subject to modifier alleles, nongenetic factors, or epigenetic factors.

A study by Hu et al indicated that in WDR35 mutation—one cause of JS—skeletal dysplasia and fetal anomalies may result from copy number variation. Moreover, down-regulation of WDR35 may lead to cilia formation damage and, sequentially, indirect Gli signal regulation, with consequent negative regulation of osteogenic differentiation. [14]