Genetics of Asphyxiating Thoracic Dystrophy (Jeune Syndrome) Clinical Presentation

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 11, 2011
 

History

Clinical presentations of lethal, severe, and latent forms of Jeune syndrome 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 Jeune syndrome have no respiratory symptoms in infancy or childhood.
  • Chest deformity of varying degree
  • Short-limbed dwarfism
  • Other symptoms: History may also reveal failure to thrive, gastroenteritis, recurrent rectal prolapse, diarrhea, congestive cardiac failure, puffy face, and ankle swelling.
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Physical

  • Dwarfism is noted.
  • Thoracic findings are as follows:
    • A long, narrow, and abnormally small thorax with reduced thoracic cage capacity; lung hypoplasia; and respiratory distress usually lead to early death.
    • The small thorax usually improves with age for those who survive early childhood.
  • Limbs exhibit variable micromelia and short digits with bulbous terminal phalanges and occasional postaxial polydactyly of the hands and feet.
  • Eyes exhibit occasional retinal degeneration.
  • Patients may have occasional intestinal malabsorption.
  • Renal failure may develop during infancy, early adolescence, or second decade of life.
  • Polyuria, polydipsia, and hypertension may be present during the second or third year of life.
  • Occasional involvement of the liver may include prolonged neonatal jaundice, polycystic liver disease, hyperplasia of the bile ducts, and congenital hepatic cirrhosis. The hepatic dysfunction includes vomiting, hyperbilirubinemia, elevated transaminases, hepatomegaly, and portal hypertension.[5]
  • Occasional involvement of the heart may include cardiac failure secondary to increased pulmonary vascular resistance, thoracic constriction, alveolar hypoplasia, and possible intrinsic myocardial disease.
  • Cystic changes of pancreatic ducts and pancreatic exocrine insufficiency may be present in long-term survivors of Jeune syndrome.
  • Occasional involvement of the teeth, nails, and other organs may occur.
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Causes

  • Jeune syndrome is known to be genetically heterogeneous. One locus is at chromosome 15q13. Another locus is at chromosome 3q24-3q26.
  • Jeune syndrome is the first chondrodysplasia to be linked to a defect in intraflagellar transport (IFT) or primary cilia function.
  • Recessive mutation in IFT80, which encodes a conserved intraflagellar transport protein, has been shown in Jeune syndrome.[6]
  • Jeune asphyxiating thoracic dystrophy is a genetically heterogeneous disorder and considered a ciliopathy.[7, 8] Beales and colleagues identified two missense mutations and an in-frame deletion in IFT80, the gene encoding the Ift80 protein, thereby linking this syndrome to ciliary dysfunction.[9] Ift80 was shown to localise to the basal body of cilia in a murine chondrocytic cell line. Aberrant Shh signalling appears to underlie the skeletal manifestations observed in IFT mutants.[10] Zebrafish morphant for ift80 demonstrate downregulation of ptc1, a Shh binding receptor. Phenotypic similarity is observed in Ihh null mice compared with patients with Jeune asphyxiating thoracic dystrophy, in that they exhibit extremely short narrow rib cages. Similarly, mice carrying a mutation in Pthrp, a gene regulated by Ihh via Gli3 during chondrocyte differentiation also have short ribs and sternum leading to a narrow rib cage.
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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG  Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

James Bowman, MD  Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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An infant with Jeune syndrome. Note the narrow chest and shortened upper extremities.
A child with Jeune syndrome. Note long narrow thorax with respiratory difficulty.
Note cystic renal dysplasia on the left kidney and renal hypoplasia on the right kidney.
Note the narrow chest and shortened ribs.
Note the shortened upper extremity with acromelic shortening.
 
 
 
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