Asphyxiating thoracic dysplasia

Asphyxiating thoracic dysplasia
Synonyms	Jeune syndrome, asphyxiating thoracic chondrodystrophy, infantile thoracic dystrophy
Pronounce
Field
Symptoms	Narrow chest, short ribs, shortened bones of the arms and legs, unusually shaped pelvis, and extra fingers and/or toes
Complications
Onset
Duration
Types
Causes
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment	Mechanical ventilation, endotracheal suctioning, postural drainage, Vertical expandable prosthetic titanium rib (VEPTR), Lateral thoracic expansion, or other chest reconstruction surgeries.
Medication
Prognosis
Frequency	1 in 100,000 to 130,000
Deaths	Mortality of affected: 60-70%

Lateral CXR of the same person above

Asphyxiating Thoracic Dysplasia (ATD), also known as Jeune Syndrome, is a rare genetic disorder characterized by skeletal abnormalities that primarily affect the thoracic region. This condition leads to a narrow, bell-shaped chest, which can restrict lung development and function, often resulting in severe respiratory distress. First described by the French pediatrician Mathis Jeune in 1955, ATD encompasses a spectrum of clinical manifestations, including:

• Narrow thorax
• Short ribs
• Shortened limbs
• Polydactyly (extra fingers and/or toes)
• Renal anomalies
• Hepatic fibrosis
• Retinal dystrophy

The incidence of ATD is estimated to be between 1 in 100,000 to 130,000 live births. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to manifest the disease.

Clinical Features

The clinical presentation of ATD is highly variable, ranging from mild forms with minimal respiratory involvement to severe cases leading to perinatal death. Key clinical features include:

Respiratory System

• Narrow, bell-shaped chest: The hallmark of ATD is a constricted thoracic cavity due to short ribs, leading to respiratory insufficiency. Newborns may present with rapid, shallow breathing and may require respiratory support.

• Pulmonary hypoplasia: Underdevelopment of the lungs is common, contributing to breathing difficulties and increased susceptibility to respiratory infections.

Skeletal System

• Shortened limbs: Both upper and lower limbs may be shorter than average, often accompanied by metaphyseal abnormalities.
• Polydactyly: Extra digits on hands and/or feet are frequently observed.
• Pelvic anomalies: Irregularities in pelvic bone development can occur, potentially affecting mobility.

Renal and Hepatic Involvement

• Renal disease: Cystic kidney disease may develop, leading to impaired kidney function or chronic kidney disease.
• Hepatic fibrosis: Liver involvement can result in fibrosis, potentially progressing to liver dysfunction.

Ocular Manifestations

• Retinal dystrophy: Progressive retinal degeneration can lead to vision impairment or blindness.

Genetic Basis

ATD is classified as a ciliopathy, a disorder arising from defects in the structure or function of cilia—microscopic, hair-like structures on the surface of cells. Mutations in several genes encoding proteins involved in ciliary function have been implicated in ATD, including:

• IFT80
• DYNC2H1
• WDR19
• IFT140
• TTC21B

These genetic mutations disrupt normal ciliary function, leading to the diverse clinical manifestations observed in ATD.

Diagnosis

Diagnosis of ATD involves a combination of clinical evaluation, imaging studies, and genetic testing:

• Clinical Evaluation: Assessment of physical characteristics such as chest shape, limb length, and presence of polydactyly.

• Imaging Studies:
  • Radiography: X-rays reveal short ribs, narrow thoracic cavity, and pelvic anomalies.
  • Ultrasonography: Prenatal ultrasound can detect characteristic skeletal abnormalities.

• Genetic Testing: Identification of mutations in genes associated with ciliary function confirms the diagnosis.

Management and Prognosis

Management of ATD is multidisciplinary, focusing on addressing respiratory, renal, and orthopedic complications:

Respiratory Support

• Mechanical ventilation: Necessary for newborns with severe respiratory distress.

• Surgical interventions: Procedures such as the implantation of vertical expandable prosthetic titanium ribs (VEPTR) can expand the thoracic cavity, improving lung capacity and function.

Renal Management

• Monitoring: Regular assessment of kidney function is essential.

• Interventions: Management of renal impairment may include medication, dialysis, or kidney transplantation in severe cases.

Orthopedic Care

• Physical therapy: Aims to improve mobility and strength.

• Surgical correction: Addressing limb deformities or polydactyly to enhance function and appearance.

Prognosis

The prognosis of ATD varies based on the severity of thoracic constriction and associated complications. Severe cases with significant respiratory involvement have a high mortality rate in infancy. However, individuals with milder forms may survive into adulthood, though they remain at risk for renal and hepatic complications.

Research and Future Directions

Ongoing research aims to better understand the genetic and molecular mechanisms underlying ATD, with the goal of developing targeted therapies. Advances in prenatal imaging and genetic testing facilitate early diagnosis, allowing for timely interventions that may improve outcomes. Additionally, innovations in surgical techniques and respiratory support continue to enhance the quality of life for individuals with ATD.

See Also

• Ciliopathy
• Skeletal dysplasia
• Polydactyly
• Pulmonary hypoplasia

External links

Classification	OMIM: 208500 DiseasesDB: 32469
External resources	eMedicine: article/945537

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