Definition

Jeune syndrome is a rare genetic disorder characterized by a small and narrow chest cavity, which limits the ability of the lungs to grow and expand properly during breathing. This abnormal chest structure (dystrophic) leads to difficulty breathing (asphyxia), and the disease is also known as asphyxiating thoracic dystrophy.

Jeune syndrome was first described in medical literature by French physician Jean Jeune in 1955. It is caused by a genetic mutation and is inherited as an autosomal recessive disorder, meaning that both parents must carry and pass on the gene mutation for the condition to develop. Jeune syndrome is an extremely rare condition.

In the United States, fewer than 5,000 people are affected by Jeune syndrome. The incidence is estimated to be 1 in 100,000 to 130,000 births. Despite its rarity, the mortality rate is high, with approximately 60-70% of affected individuals dying from respiratory failure during infancy or early childhood.

Causes

Jeune syndrome is most commonly caused by genetic mutations in at least 11 different genes, including the IFT80 and DYNC2H1 genes. The presence of multiple genes involved in this condition means that the severity of the disease can vary significantly from one individual to another. These genes are responsible for producing various proteins found in cilia, which are finger-like structures on the surface of body cells. Cilia play a crucial role in a process known as intraflagellar transport (IFT), where important materials are moved into and out of the cilia to enable their normal function.

Mutations associated with Jeune syndrome disrupt IFT, impairing the formation or normal function of cilia in various cells throughout the body. Cilia are essential in regulating many chemical signaling pathways, such as the Sonic Hedgehog pathway, which is involved in cell division and the development of mature cells, especially in cartilage and bone cells.

Disruptions in this signaling pathway lead to bone abnormalities, particularly affecting the bones that form the chest cavity. In addition to bones, abnormal cilia can be found in other organs like the kidneys, liver, and retina, resulting in dysfunction in these organs.

Risk Factor

There are no known specific risk factors for Jeune syndrome. This condition is inherited in an autosomal recessive manner, meaning a child will develop the disease if they inherit one copy of the mutated gene from each parent.

Symptoms

The symptoms of Jeune syndrome can vary widely between individuals. Symptoms may be apparent at birth or become noticeable as the child grows, usually around 4 to 5 years of age. Common signs and symptoms include:

• Small and narrow chest wall: Individuals with Jeune syndrome have a bell-shaped chest with reduced capacity for lung expansion.

• Respiratory distress: The abnormal chest wall shape can cause respiratory distress. The severity varies with the disease's progression. Children with milder forms may experience only shortness of breath, while more severe cases can lead to repeated lung infections (pneumonia) or even respiratory failure requiring assistance.

• Internal organ issues: About 40% of people with Jeune syndrome experience kidney complications, including frequent urination or, in severe cases, kidney failure. Around 30% of cases involve liver problems, leading to jaundice and an enlarged liver. The condition can also affect other organs such as the eyes, heart, and digestive system.

• Bone and joint abnormalities: Individuals with Jeune syndrome often have a small stature with short arms and legs. They may also have short fingers or toes (brachydactyly) or extra digits (polydactyly).

Severe respiratory issues typically occur early in life, although some cases may have milder respiratory symptoms with more significant kidney or digestive system complications.

Diagnosis

To diagnose Jeune syndrome, the doctor will begin by gathering information from the patient's family regarding the medical history and any family history of the condition. A physical examination will be performed to assess the degree of respiratory distress and to identify other abnormalities associated with Jeune syndrome, such as a small, narrow, bell-shaped chest cavity, short arms and legs, extra or shortened fingers, and issues with organs like the liver, kidneys, and eyes.

Following this, the doctor will recommend diagnostic tests to confirm the diagnosis. These may include imaging tests like X-rays, CT scans, or MRIs, as well as blood and urine tests. Genetic testing may also be advised to further support the diagnosis.

For families at risk, an ultrasound examination during the second and third trimesters of pregnancy can help detect the condition. Features visible in this examination include a narrow chest wall, short ribs, and short long bones. Additional ultrasound signs, such as polyhydramnios (excessive amniotic fluid) and limited or absent fetal chest movement during intrauterine breathing, can also be associated with Jeune syndrome.

Management

Treatment for Jeune syndrome depends on the severity of symptoms and the affected organs. The focus of treatment is supportive, aiming to reduce the severity of symptoms. Therapy is primarily centered on managing and preventing respiratory infections.

Treatment options for Jeune syndrome include:

Non-Surgical Treatment

Because breathing problems are common in babies with Jeune syndrome, doctors may provide supplemental oxygen and use a ventilator to assist with breathing. In severe cases, babies may need to be connected to a ventilator for ongoing respiratory support.

Antibiotics may be prescribed to address any respiratory infections, and if kidney failure is present, dialysis therapy might be required.

Surgical Treatment

Surgical procedures are generally considered only for severe cases. If non-surgical treatments fail and the baby is at risk of death, surgery may be needed to enlarge the chest cavity and prevent further lung damage.

Several surgical techniques can be used to correct chest wall abnormalities, with the most common being the Vertical Expandable Prosthetic Titanium Rib (VEPTR). This method involves placing titanium implants into the ribs to expand the chest cavity.

However, chest wall surgery carries significant risks and can be quite challenging. It's crucial to consult with a surgeon to discuss the potential risks associated with the surgery.

Prevention

Jeune syndrome is a genetic condition that cannot be prevented. Since it is inherited in an autosomal recessive manner, couples with a family history of Jeune syndrome are advised to consult with a doctor and a genetic counselor. This can help them understand the risks and potential treatment options when planning to have a child.

When to See a Doctor?

Jeune syndrome is typically identifiable at birth, with specific abnormalities like small stature, short arms and legs, a bell-shaped chest, and extra digits (polydactyly) on the hands or feet. Immediate recognition and treatment are often possible at birth.

In milder cases, however, babies may not show the typical abnormalities. It's important to be aware of other associated signs of the condition. Babies with Jeune syndrome may experience respiratory issues ranging from shortness of breath to complete respiratory failure.

If your child exhibits respiratory problems or limb abnormalities associated with Jeune syndrome, seek medical attention immediately.

Looking for more information about other diseases? Click here!