OVERVIEW

What is Jeune Syndrome?

Jeune Syndrome (JS), also known as Asphyxiating Thoracic Dystrophy (ATD), is an extremely rare genetic disorder characterized by skeletal dysplasia.

Patients primarily exhibit severe underdevelopment of the chest, presenting with a narrow cylindrical or bell-shaped rib cage. Beyond infancy, the ribs continue to grow horizontally, restricting outward expansion of the chest. As a result, the lungs can only expand downward and cannot fully inflate.

Without proper respiratory support, most patients develop respiratory failure within the first year of life. They are also prone to recurrent lung infections, which are the leading cause of death.

The prognosis is poor, and even if patients survive, their quality of life is significantly impacted.

Is Jeune Syndrome a rare disease?

Yes.

It occurs in approximately 1 in 100,000 to 130,000 live births. In May 2018, the disease was included in the First List of Rare Diseases jointly issued by China's National Health Commission and four other government departments.

SYMPTOMS

What are the clinical manifestations of Jeune syndrome patients?

• Patients typically have a very narrow and small chest, experience varying degrees of breathing difficulties from birth, and suffer from recurrent lung infections.

• Pelvic dysplasia, short limbs, short stature, and possible polydactyly.

• Most patients develop severe respiratory failure within the first two years of life, leading to death in 60%–80% of cases. Survivors may suffer from kidney, liver, pancreatic, or retinal damage.

• Kidney damage primarily manifests as polyuria, proteinuria, elevated blood urea nitrogen and creatinine levels, and hypertension.

• Liver damage mainly includes portal hypertension, hepatomegaly, cholestasis, conjugated hyperbilirubinemia, cirrhosis, and elevated liver enzymes.

• Ocular damage includes optic nerve hypoplasia, retinal dystrophy, abnormal retinal pigmentation, nystagmus, myopia, and progressive visual impairment.

• Pancreatic damage primarily presents as cystic changes with fibrosis.

CAUSES

What are the causes of Jeune syndrome?

Patients exhibit similar clinical manifestations, but the disease-causing genes may differ among individuals, a phenomenon known as genetic heterogeneity. Jeune syndrome is a genetically heterogeneous disorder with complex causes that are not yet fully understood.

To date, researchers have identified mutations in dozens of genes associated with the development of Jeune syndrome. Studies indicate that the most frequently mutated gene is DYNC2H1 (OMIM 603297), which encodes a protein critical for skeletal development and also plays important roles in other tissues, including the kidneys, liver, bile ducts, and retina.

In patients with confirmed genetic mutations, Jeune syndrome typically follows an autosomal recessive inheritance pattern.

Jeune syndrome is a relatively rare autosomal recessive disorder. What is autosomal recessive inheritance?

Autosomal recessive disorders exhibit a horizontal inheritance pattern, meaning multiple affected individuals may be found among siblings, but not in parents or ancestors. The number of affected males and females is roughly equal, with no significant difference.

If a couple has already had a child with an autosomal recessive disorder, the probability of having another child with the same condition in a subsequent pregnancy is 25%, while the chance of having a child who is a carrier (unaffected but carrying the disease-causing gene) is 50%.

DIAGNOSIS

How is Jeune Syndrome Diagnosed?

Diagnosis can be made based on the child's symptoms, physical examination, chest X-ray, CT scan, and pulmonary function tests. Specific criteria include:

• Narrow chest, rapid breathing with abdominal breathing, and minimal or no chest expansion. Recurrent lung infections, pelvic dysplasia, short limbs, short stature, polydactyly (extra fingers/toes), and possible liver, kidney, pancreatic, or visual dysfunction.

• Physical examination reveals irregular breathing rhythm, narrow chest circumference, increased respiratory rate, short limbs, and palpable liver/spleen below the costal margin.

• Obstetric ultrasound after 20 weeks of pregnancy shows short femur and small chest in the fetus.

• Infant X-rays reveal a narrow chest, horizontally short ribs, elevated clavicles, cardiothoracic ratio >0.5, and trident-shaped pelvis. Chest CT shows skeletal dysplasia and pulmonary atelectasis. Pulmonary function tests indicate small lung volume, low residual volume, and reduced airway compliance.

TREATMENT

Which department should Jeune syndrome patients visit?

Patients can seek diagnosis and treatment in pediatrics, cardiothoracic surgery, orthopedics, or respiratory medicine departments at hospitals with treatment capabilities.

How is Jeune syndrome treated?

• Respiratory support: Provide oxygen promptly if respiratory distress occurs. In critical cases, mechanical ventilation (including non-invasive ventilation, invasive ventilation, or tracheostomy) may be administered. To help patients tolerate mechanical ventilation, doctors may prescribe appropriate sedatives, which can also alleviate anxiety and reduce tracheal secretions.

• Treating pulmonary infections: In cases of lung infection, doctors will select appropriate antibiotics and monitor blood tests, inflammatory markers, and changes in chest CT scans.

• Correcting electrolyte imbalances: Maintain stable internal homeostasis.

• Monitoring organ function: Regularly assess the condition of the lungs, heart, kidneys, liver, and pancreas, and provide supportive treatment for organ damage.

• Nutritional support: Maintain a balanced diet. If oral intake is impaired during illness, enteral or parenteral nutrition may be provided. Enteral nutrition delivers nutrients via the gastrointestinal tract, while parenteral nutrition supplies essential nutrients intravenously.

Does Jeune syndrome require surgery?

Yes. Surgical intervention can correct thoracic deformities and alleviate respiratory distress symptoms.

Surgical correction methods include: median sternotomy, rib distraction sternoplasty, modified Nuss procedure, lateral thoracic expansion (LTE), and vertical expandable prosthetic titanium rib (VEPTR) implantation.

• Median sternotomy: Involves implanting autologous or donor bone to increase chest circumference and allow better expansion. This procedure has low success rates in infants under one year old and may lead to acquired thoracic rigidity, often requiring multiple surgeries.

• Rib distraction sternoplasty: Improves lung compliance, average airway pressure, and intrathoracic compliance, enhancing ventilation.

• Modified Nuss procedure: A minimally invasive surgery suitable for older children with mild Jeune syndrome, serving as an alternative to more traumatic corrective methods.

• Lateral thoracic expansion (LTE): A relatively safe treatment option for children with Jeune syndrome over one year old.

• Vertical expandable prosthetic titanium rib (VEPTR): Helps maintain thoracic mobility, volume, and diaphragm function in affected children.

DIET & LIFESTYLE

What should children with Jeune syndrome pay attention to in daily life and diet?

• Avoid strenuous exercise to prevent worsening breathing difficulties.

• Families of children with Jeune syndrome should receive genetic counseling and education, focusing on the severity of the condition, the risks and benefits of treatment, and the lifelong needs of patients with Jeune syndrome.

• Children with Jeune syndrome often experience discomfort and anxiety due to respiratory distress, requiring comfort and reassurance from family and social support, with medication if necessary.

• No special dietary restrictions are required; a balanced and nutritious diet is sufficient.

Does Jeune syndrome require follow-up examinations?

Yes.

• First, children with Jeune syndrome need routine physical examinations during the first two years after birth.

• Second, regular follow-ups should include liver and kidney function tests, ophthalmologic examinations, abdominal ultrasound, pulmonary function tests, and sleep monitoring, even if symptoms are mild.

PREVENTION

Can Jeune Syndrome Be Prevented?

Jeune syndrome is caused by genetic mutations, so once a child is born, the onset of the disease cannot be avoided. To prevent Jeune syndrome, necessary genetic counseling, prenatal diagnosis, and prenatal checkups are required.

• Genetic Counseling: If there is a history of Jeune syndrome in the family, other members should undergo genetic counseling first to assess the risk of offspring inheriting the condition before deciding whether to have children.
• Prenatal Diagnosis: For those already pregnant, prenatal diagnosis through genetic testing can be performed to terminate the pregnancy in time and prevent the birth of an affected fetus.
• Regular Prenatal Checkups: During pregnancy, regular prenatal checkups and obstetric ultrasound examinations are necessary to detect fetal deformities and abnormalities early.