junctional epidermolysis bullosa, LAMA3-related

What is Junctional Epidermolysis Bullosa, LAMA3-related?

Junctional epidermolysis bullosa (JEB), LAMA3-related, is an inherited disease that causes severe blistering on the skin. This condition has two subtypes: Herlitz JEB (H-JEB) and non-Herlitz JEB (NH-JEB). Both forms of JEB are caused by harmful changes (variants) in the LAMA3 gene.

Herlitz Junctional Epidermolysis Bullosa (H-JEB)

Individuals with H-JEB lack anchors to hold the layers of their skin together. They 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.

Other symptoms in infants and children with the disease may include a hoarse cry, cough, other breathing problems, fevers, loss of fingernails and toenails, poorly formed tooth enamel, abnormalities of the urinary tract and bladder, poor growth, electrolyte imbalance, hair loss, osteoporosis, and skin cancer.

Non-Herlitz Junctional Epidermolysis Bullosa (NH-JEB)

NH-JEB 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, and poorly formed tooth enamel are observed in individuals with NH-JEB.

Laryngo-onycho-cutaneous (LOC) syndrome

A rare subtype of JEB known as laryngo-onycho-cutaneous (LOC) syndrome is also caused by harmful genetic changes in the LAMA3 gene. Infants with the condition 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.

How common is Junctional Epidermolysis Bullosa, LAMA3-related?

H-JEB is extremely rare; less than 1 in 1 million individuals are affected by H-JEB.

NH-JEB is slightly more common, with an estimated 1 in 500,000 individuals affected by the disease.

The incidence of LOC syndrome is not known.

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. Antibiotics and antiseptics are often prescribed to prevent and treat infections. A dietitian should be consulted for individuals with H-JEB to ensure proper nutrition. To avoid dehydration, individuals should drink plenty of fluids.

In individuals with breathing difficulty (typically those with H-JEB), an opening may be made in the neck to deliver air to the trachea (tracheostomy).

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

The prognosis for individuals with all forms of junctional epidermolysis bullosa, LAMA3-related, is poor. The disease is extremely painful, and causes of death often include impaired physical growth (failure to thrive), infection, and respiratory failure. Approximately 40-45% of individuals with either form of JEB die in the first year of life. Approximately 62% of individuals with H-JEB and 48% of individuals with NH-JEB die by age 15. The exact life expectancy for individuals with LOC is not well known, but is expected to be similar to the other forms of JEB.