eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Asphyxiating Thoracic Dystrophy (Jeune Syndrome)

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
Contributor Information and Disclosures

Updated: Jun 10, 2009

Introduction

Background

  • In 1955, Jeune et al described familial asphyxiating thoracic dystrophy in a pair of siblings with severely narrow thoraxes.
  • This condition is also known as Jeune syndrome. Jeune syndrome, a potentially lethal congenital dwarfism, is a rare autosomal recessive disorder characterized by typical skeletal dysplasias, such as a narrow thorax and micromelia, with respiratory and renal manifestations.1,2 Respiratory symptoms widely vary from respiratory failure and infantile death to latent phenotype without respiratory symptoms.

    An infant with Jeune syndrome. Note the narrow ch...

    An infant with Jeune syndrome. Note the narrow chest and shortened upper extremities.

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    An infant with Jeune syndrome. Note the narrow ch...

    An infant with Jeune syndrome. Note the narrow chest and shortened upper extremities.



    A child with Jeune syndrome. Note long narrow tho...

    A child with Jeune syndrome. Note long narrow thorax with respiratory difficulty.

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    A child with Jeune syndrome. Note long narrow tho...

    A child with Jeune syndrome. Note long narrow thorax with respiratory difficulty.



    Note the shortened upper extremity with acromelic...

    Note the shortened upper extremity with acromelic shortening.

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    Note the shortened upper extremity with acromelic...

    Note the shortened upper extremity with acromelic shortening.

Pathophysiology

  • Classic manifestations in infancy include dwarfism with short ribs, short limbs, and characteristic radiographic changes in the ribs and pelvis. The severity of clinical and radiographic features varies.
  • All patients have small chests, but the degree of the respiratory distress varies from negligible to rapidly fatal.
  • Lung hypoplasia, presumably due to a restricted thoracic cage, is the major cause of death in infancy.
  • Patients who survive the newborn period may later develop renal and pancreatic insufficiency.3
  • Variability in clinical, radiographic, and pathological manifestations may be related to genetic heterogeneity.

Frequency

United States

  • Incidence is estimated at 1 case per 100,000-130,000 live births.4

Mortality/Morbidity

  • Although Jeune syndrome may be associated with bilateral microcystic renal disease, which may gradually progress to tubular atrophy and renal failure, the most common and prominent clinical presentation is alveolar hypoventilation. Alveolar hypoventilation is caused by impaired chest expansion as a result of short horizontally placed ribs.
  • Furthermore, most patients with Jeune syndrome (approximately 60-70%) die from respiratory failure in early infancy and early childhood. Chronic renal failure may ensue in survivors.
  • Few patients reach adolescence or adulthood.

Race

  • Jeune syndrome has no race predilection.

Sex

  • The syndrome is not associated with any sex predilection.

Age

  • Jeune syndrome may be detected at birth or during infancy because of typical clinical and radiographic signs.

Clinical

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.

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.

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

More on Asphyxiating Thoracic Dystrophy (Jeune Syndrome)

Overview: Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Differential Diagnoses & Workup: Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Treatment & Medication: Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Follow-up: Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Multimedia: Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
References
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References

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Further Reading

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Keywords

asphyxiating thoracic dystrophy, Jeune syndrome, Jeune's syndrome, asphyxiating thoracic dysplasia, infantile thoracic dystrophy, thoracic-pelvic-phalangeal dystrophy, severely narrow thorax, congenital dwarfism, skeletal dysplasia, lung hypoplasia, renal lesions, renal failure, Jeune bilateral microcystic renal disease, tubular atrophy, alveolar hypoventilation, respiratory failure, respiratory distressed, gastroenteritis, failure to thrive, neonatal jaundice, polycystic liver disease, treatment, diagnosis 

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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 Medical Association, American Society of Human Genetics, and Teratology Society
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, 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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