junctional epidermolysis bullosa, LAMA3-related

What is Junctional Epidermolysis Bullosa, LAMA3-related?

Junctional epidermolysis bullosa (JEB), LAMA3-related, is an inherited disease characterized by severe skin blistering. It is caused by harmful genetic changes (variants) in the LAMA3 gene. The LAMA3 gene helps create anchors that hold the layers of their skin together. Harmful changes in the gene can alter this ability to hold together skin layers, leading to the symptoms seen with this disorder.

JEB, LAMA3-related can be classified into three forms: severe JEB (previously called JEB Herlitz or generalized severe JEB), intermediate JEB (previously called JEB non-Herlitz or generalized intermediate JEB), and Laryngo-onycho-cutaneous (LOC) syndrome. In some cases, it may be possible to predict which form an individual will likely have based on their specific LAMA3 variants.

Severe Junctional Epidermolysis Bullosa

Individuals with this form of JEB develop large, fluid-filled blisters in response to any trauma, even something as minor as increased room temperature. Internal blistering on the lining of the nose, mouth, esophagus, trachea, rectum, stomach, intestines, and eyes is also present from birth.

Granulation tissue, a soft, pink, bumpy, moist skin, forms at blistering sites in the healing process. It is also seen around the nose, mouth, ears, fingers, and toes, as well as in areas that receive friction, such as the buttocks and back of the head. Because this tissue can chafe and wear away, it bleeds easily and can be a site of fluid loss or infection.

Individuals often have dental abnormalities due to a poorly formed outer tooth coating (amelogenesis imperfecta). Other symptoms in infants and children with the disease may include a hoarse cry, cough, other breathing problems, fevers, loss of fingernails and toenails, abnormalities of the urinary tract and bladder, poor growth, electrolyte imbalance, hair loss, osteoporosis, and a specific type of skin cancer (squamous cell carcinoma).

Intermediate Junctional Epidermolysis Bullosa

This is a less severe form of JEB. Blistering occurs in fewer areas (hands, feet, knees, and elbows) and may not result in blistering of the internal organs. The onset of blistering can be later as well. Issues related to granulation tissue and complications with breathing are not common. Hair loss, improper nail formation, skin cancer (squamous cell carcinoma), and amelogenesis imperfecta are observed in individuals with intermediate JEB.

Laryngo-onycho-cutaneous (LOC) syndrome

Infants with LOC syndrome have a hoarse cry due to sores (ulcers) and granulation tissue in the voicebox (larynx). The symptom that makes LOC syndrome distinct from the other forms of JEB is that the granulation tissue often grows in the eyes. Individuals with LOC syndrome often develop vision and breathing problems. Other symptoms can include missing patches of skin and abnormally developed nails and teeth.

Additional considerations for carriers

Most carriers do not experience any symptoms. Rarely, they may have dental problems such as discoloration and tooth decay (amelogenesis imperfecta).

How common is Junctional Epidermolysis Bullosa, LAMA3-related?

Several genes are known to cause JEB, which has an incidence of 1 in 275,000 and 1 in 400,000 births. Approximately 9% of JEB is caused by LAMA3.

How is Junctional Epidermolysis Bullosa, LAMA3-related treated?

There is no cure for JEB. Symptoms are generally treated as they arise. It is best to protect children with the condition from skin damage as much as possible. For example, a cesarean section may be recommended to protect the child from the skin trauma of a vaginal birth. Affected children must avoid any movement or clothing that could damage the skin. When open wounds and blistered skin occur, they are often covered with multiple layers of non-adhesive bandages. A special gel (Filsuvez® or birch triterpenes) can be applied to the skin to help with wound healing. Antibiotics and antiseptics are often prescribed to prevent and treat infections. A dietitian may be needed to ensure proper nutrition. To avoid dehydration, individuals should drink plenty of fluids. In individuals with breathing or feeding difficulty, surgical procedures to place breathing or feeding tubes may be required.

What is the prognosis for an individual with Junctional Epidermolysis Bullosa, LAMA3-related?

The prognosis for individuals with severe JEB is poor. Most children with severe JEB do not survive past the two years of life. Causes of death often include impaired physical growth (failure to thrive), infection, and respiratory failure. Many individuals with intermediate JEB survive into adulthood, with the average age of death in the 50s or 60s.