Jeune Syndrome
Jeune Syndrome
Jeune syndrome, also known as asphyxiating thoracic dystrophy (ATD), is a rare genetic disorder characterized by a small, narrow chest and short ribs. It belongs to the group of skeletal ciliopathies, disorders affecting the development and function of cilia in various organs.
Key Points:
- Autosomal recessive inheritance
- Caused by mutations in genes involved in ciliary function
- Prevalence: Estimated at 1 in 100,000 to 1 in 130,000 live births
- Characterized by a narrow, bell-shaped thorax and short ribs
- Affects multiple organ systems: respiratory, skeletal, renal, hepatic, and retinal
- Wide spectrum of clinical severity, from lethal in infancy to milder forms surviving to adulthood
Clinical Features
Respiratory Manifestations:
- Respiratory insufficiency due to restricted thoracic capacity
- Recurrent respiratory infections
- Pneumonia
- Atelectasis
Skeletal Abnormalities:
- Narrow, bell-shaped thorax
- Short ribs with expanded anterior ends
- Short limbs (rhizomelic shortening)
- Polydactyly (in some cases)
- Pelvic abnormalities (trident acetabulum)
Renal Involvement:
- Nephronophthisis
- Cystic renal disease
- Renal insufficiency (often develops in childhood or adolescence)
Hepatic Features:
- Hepatic fibrosis
- Portal hypertension
- Bile duct proliferation
Ocular Findings:
- Retinal dystrophy (in some cases)
Other Features:
- Growth retardation
- Pancreatic cysts or fibrosis (rare)
- Dental abnormalities
Diagnosis
Diagnosis of Jeune syndrome is based on clinical features, radiographic findings, and genetic testing.
Clinical Diagnosis:
- Presence of characteristic thoracic abnormalities
- Respiratory distress in infancy
- Associated skeletal abnormalities
Radiographic Findings:
- Narrow, bell-shaped thorax with short, horizontally oriented ribs
- Elevated and fixed clavicles
- Short iliac bones with trident-shaped acetabular roofs
- Irregular metaphyseal ends of long bones
Genetic Testing:
- Next-generation sequencing panel for known Jeune syndrome genes
- Whole exome or genome sequencing if panel is negative
Additional Investigations:
- Pulmonary function tests
- Renal ultrasound and function tests
- Liver function tests and abdominal ultrasound
- Ophthalmologic examination
Differential Diagnosis:
- Other skeletal dysplasias (e.g., Ellis-van Creveld syndrome, short-rib polydactyly syndromes)
- Other ciliopathies (e.g., Sensenbrenner syndrome, Mainzer-Saldino syndrome)
- Thoracolaryngopelvic dysplasia (Barnes syndrome)
Management
Management of Jeune syndrome is multidisciplinary and focuses on supportive care and addressing specific organ system involvement.
Respiratory Management:
- Mechanical ventilation for severe cases in infancy
- Oxygen therapy
- Aggressive treatment of respiratory infections
- Chest physiotherapy
- Surgical interventions:
- Lateral thoracic expansion
- Vertical expandable prosthetic titanium rib (VEPTR) implantation
Orthopedic Management:
- Physical therapy to improve mobility
- Orthopedic surgeries for limb deformities if needed
Renal Management:
- Regular monitoring of renal function
- Management of chronic kidney disease
- Renal replacement therapy in advanced cases
Hepatic Management:
- Monitoring of liver function
- Management of portal hypertension if present
- Liver transplantation in severe cases
Ophthalmologic Care:
- Regular eye examinations
- Management of retinal dystrophy if present
Other Management Aspects:
- Nutritional support to promote growth
- Genetic counseling for families
- Psychosocial support
- Regular follow-up with a multidisciplinary team
Genetics
Inheritance Pattern:
- Autosomal recessive
Genetic Basis:
- Multiple genes identified, all involved in ciliary structure or function
- Common genes include:
- IFT80
- DYNC2H1 (most frequent cause)
- TTC21B
- WDR19
- IFT140
Genotype-Phenotype Correlations:
- Variable expressivity, even within families
- Some correlations observed:
- DYNC2H1 mutations: often associated with more severe phenotypes
- IFT140 mutations: higher risk of renal and retinal involvement
Molecular Mechanisms:
- Dysfunction of primary cilia
- Impaired intraflagellar transport (IFT)
- Defects in ciliary structure and/or protein trafficking
- Disruption of key developmental signaling pathways (e.g., Hedgehog pathway)
Genetic Testing Considerations:
- Multi-gene panel testing as first-line approach
- Whole exome or genome sequencing for unsolved cases
- Importance of genetic diagnosis for prognosis and family planning
- Prenatal genetic testing possible for at-risk pregnancies
