SNP Shot: Genomic Insights

Junctional epidermolysis bullosa (JEB) is a significant type of epidermolysis bullosa (EB), a group of inherited disorders characterized by extremely fragile skin that blisters easily. Even minor trauma, like rubbing or scratching, can cause blisters and skin erosions. JEB is broadly classified into two categories: JEB generalized severe (formerly Herlitz JEB) and JEB generalized intermediate (formerly non-Herlitz JEB). While these types differ in their severity, they share many clinical features and can result from mutations in the same genes.

JEB generalized severe represents the more severe end of the spectrum. Individuals with this form experience widespread blistering from birth or early infancy, affecting large areas of the body. Mucous membranes, such as those lining the mouth and digestive tract, are also affected, leading to difficulties with eating and digestion. Consequently, affected children often suffer from malnutrition and impaired growth. The extensive blistering can result in scarring and the development of granulation tissue, characterized by red, bumpy patches that bleed easily. This can lead to serious infections and the loss of vital proteins, minerals, and fluids in affected infants. Furthermore, granulation tissue buildup in the airways can cause a weak, hoarse cry and breathing problems.

JEB generalized severe can also lead to other complications, including fusion of the fingers and toes, nail abnormalities, joint contractures that restrict movement, hair loss (alopecia), and enamel hypoplasia (thinning of tooth enamel). Due to the severity of these signs and symptoms, infants with JEB generalized severe typically have a short lifespan, often not surviving beyond their first year.

JEB generalized intermediate is the milder form of junctional epidermolysis bullosa. Blistering in this type may be localized to the hands, feet, knees, and elbows, and often improves after the newborn period. Hair loss, abnormal nails, and irregular tooth enamel are also common features. Extensive scarring and granulation tissue formation are uncommon, resulting in rarer occurrences of breathing difficulties and other severe complications. Individuals with JEB generalized intermediate typically have a normal life expectancy.

Inheritance:

Both JEB types follow an autosomal recessive inheritance pattern. This means that both copies of the relevant gene in each cell must carry a mutation for the condition to manifest. Parents of a child with an autosomal recessive condition are carriers, possessing one copy of the mutated gene, but they usually do not exhibit any symptoms of the condition themselves. In rare instances, individuals carrying a single mutated copy of the COL17A1, LAMA3, or LAMB3 gene may present with irregular tooth enamel.