epidermolysis bullosa simplex 6, generalized, with scarring and hair loss

Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss is a skin disorder characterized primarily by abnormal blistering of the skin, hypopigmentation, and dermal atrophy, along with distinctive scarring and changes in hair distribution. The condition is associated with pathogenic variants in the KLHL24 gene, which plays an important role in maintaining skin integrity. It follows an autosomal dominant inheritance pattern, meaning that an affected individual has a 50% chance of passing the condition on to their children. This condition is very rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation is marked by consistent skin findings such as abnormal blistering, hypopigmentation, dermal atrophy, and diffuse palmoplantar hyperkeratosis, which are always present in affected individuals. In addition, some individuals experience variable features including different degrees of alopecia and onychogryphosis of the toenails, with scalp hair loss occurring in a smaller subset. These features may be noticeable early in life and can evolve over time, while the severity of symptoms can vary considerably from person to person. Not all individuals experience every feature, and variability is common in the presentation.

The condition is linked to changes in the KLHL24 gene, a gene that contributes to the structural integrity of the skin. Disruption of normal KLHL24 function is thought to compromise skin strength and resilience, leading to blistering and scarring. It is inherited in an autosomal dominant pattern, so a single copy of the altered gene is enough to cause the condition, and affected individuals have a 50% chance of passing the variant on to their offspring. Even among family members with the same genetic change, the severity and specific symptoms can vary considerably (variable expressivity).

Currently, management focuses on supportive care and symptom management tailored to the individual’s needs, as there are no approved treatments specifically targeting this condition. A multidisciplinary team is often involved in care, which may include dermatologists and other specialists to manage skin integrity, scarring, and hair loss. Genetic counseling is recommended to help affected individuals and their families understand the inheritance pattern and make informed decisions about family planning. Patients should discuss treatment options with their healthcare team to determine which approaches may be most beneficial for their particular situation.

The long‐term outlook for individuals with this condition varies, with outcomes influenced by the severity of skin involvement and overall management. With current standards of care, many individuals are able to manage symptoms effectively, although the condition may progress or remain stable over time. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialist centers to better understand the variability of the condition and to receive support for managing symptoms.