SNP Shot: Genomic Insights

Dystrophic epidermolysis bullosa (DEB) is a major type of epidermolysis bullosa (EB), a group of genetic disorders characterized by extremely fragile skin that blisters easily. Even minor injuries or friction, like rubbing or scratching, can cause blisters and skin erosions to develop. The severity of DEB varies considerably among individuals. Some individuals experience mild symptoms with blisters primarily on the hands, feet, knees, and elbows. Others have severe widespread blistering, potentially leading to vision loss, significant scarring, and other serious health problems.

DEB is classified into different subtypes based on inheritance patterns and specific features, although these subtypes often overlap and are all caused by mutations in the same gene.

Recessive dystrophic epidermolysis bullosa severe generalized (RDEB-sev gen) is the most severe and classic form of DEB. Infants with RDEB-sev gen typically present at birth with extensive blistering and areas of missing skin, often due to birth trauma. Blisters commonly appear all over the body, including mucous membranes like the mouth and digestive tract lining. Healing of these blisters leads to severe scarring. Scarring in the mouth and esophagus can cause difficulty chewing and swallowing, leading to chronic malnutrition and impaired growth. Further complications from ongoing scarring include fusion of fingers and toes, loss of fingernails and toenails, joint contractures that limit movement, and eye inflammation that can result in vision loss. People with RDEB-sev gen also have a significantly increased risk of developing an aggressive and often life-threatening form of skin cancer called squamous cell carcinoma in early adulthood.

Other recessive forms of DEB, referred to as RDEB-generalized and localized (RDEB-gen and -loc), represent a spectrum of severity. These forms are less severe than RDEB-sev gen and are distinguished by the affected body regions. In milder cases, blistering may be confined to the hands, feet, knees, and elbows, while more severe cases involve widespread blistering. Rare forms may affect specific areas like the shins or abdomen. Affected individuals often have deformed fingernails and toenails. While RDEB-gen and -loc involve scarring in blistered areas, the scarring is less severe than that seen in RDEB-sev gen.

Dominant dystrophic epidermolysis bullosa (DDEB) is another major type of DEB. The symptoms of DDEB are generally milder than those of the recessive forms. Blistering is frequently limited to the hands, feet, knees, and elbows. Scarring occurs after blister healing, but it is less severe compared to the recessive forms. Most individuals with DDEB have malformed fingernails and toenails, which may eventually be lost. In the mildest cases, the only sign of DDEB may be abnormal nails.

Inheritance:

Recessive dystrophic epidermolysis bullosa (RDEB-sev gen and RDEB-gen and -loc) follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated COL7A1 gene, one from each parent, to develop the condition. Parents are typically carriers who each have one copy of the mutated gene but do not exhibit symptoms themselves.

DDEB follows an autosomal dominant inheritance pattern. This means that only one copy of the altered COL7A1 gene is needed in each cell to cause the disorder. Approximately 70% of individuals with DDEB inherit the altered gene from an affected parent. The remaining 30% develop the condition due to a new mutation in the COL7A1 gene, occurring in individuals with no family history of the disorder.