Dominant dystrophic epidermolysis bullosa

Alternate names

Dominant dystrophic epidermolysis bullosa, generalized; DDEB, generalized; DDEB-gen; Epidermolysis bullosa dystrophica, autosomal dominant; Dystrophic epidermolysis bullosa, autosomal dominant; Epidermolysis bullosa dystrophica, Cockayne-Touraine type (formerly); Epidermolysis bullosa dystrophica, Pasini type (formerly); Autosomal dominant dystrophic epidermolysis bullosa, Pasini and Cockayne-Touraine types; DDEB, Pasini and Cockayne-Touraine types; Generalized dominant dystrophic epidermolysis bullosa

Definition

Dominant dystrophic epidermolysis bullosa (DDEB) is a type of epidermolysis bullosa (EB), which is a group of rare inherited conditions in which the skin blisters extremely easily.

Cause

• Dominant dystrophic epidermolysis bullosa (DDEB) is caused by mutations in the COL7A1 gene.
• The COL7A1 gene provides instructions for making a protein that is used to assemble type VII collagen.
• Collagen gives structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body.
• Type VII collagen plays an important role in strengthening and stabilizing the skin.
• It is the main component of structures called anchoring fibrils, which anchor the top layer of skin, called the epidermis, to an underlying layer called the dermis.

Gene mutations

• COL7A1 mutations alter the structure or disrupt the production of type VII collagen, which impairs its ability to help connect the epidermis to the dermis.
• When type VII collagen is abnormal or missing, friction or other minor trauma can cause the two skin layers to separate.
• This separation leads to the formation of blisters, which can cause extensive scarring as they heal.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• Dominant dystrophic epidermolysis bullosa (DDEB) has an autosomal dominant pattern of inheritance.
• Autosomal dominant inheritance means that one copy of the gene with the mutation in each cell is sufficient to cause the disorder.
• About 70 percent of individuals with DDEB have inherited a COL7A1 mutation from an affected parent.
• The remaining 30 percent have the condition as a result of a new (de novo) mutation in the COL7A1 gene.
• These cases occur in people with no history of the disorder in their family.
• Regardless of whether an individual with an autosomal dominant condition has inherited the mutation or has a new mutation, each child of the affected individual has a 50% (1 in 2) chance of also having the condition, and a 50% chance of not having the condition.

Signs and symptoms

• Dominant dystrophic epidermolysis bullosa (DDEB) is consivered to be a more mild form of dystrophic epidermolysis bullosa (DEB).
• Blistering is often limited to the hands, feet, knees, and elbows.
• Blistering may be relatively benign, but still heals with scarring and milia.
• Dystrophic nails, especially toenails, are common and loss of nails may occur.
• In the mildest forms, dystrophic nails may be the only characteristic noted.
• Blistering in DDEB often improves somewhat with age.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Acral blistering
• Dystrophic toenail(Poor toenail formation)
• Fragile skin(Skin fragility)
• Milia(Milk spot)

5%-29% of people have these symptoms

• Absent fingernail
• Absent toenail
• Atrophic scars(Sunken or indented skin due to damage)
• Dystrophic fingernails(Poor fingernail formation)
• Erosion of oral mucosa
• Oral mucosal blisters(Blisters of mouth)
• Recurrent loss of toenails and fingernails(Recurrent shedding of toenails and fingernails)
• Skin erosion

Diagnosis

• The diagnosis of DEB is established in a proband with characteristic clinical findings and the identification of biallelic pathogenic variants (RDEB) or a heterozygous pathogenic variant (DDEB) in COL7A1 by molecular genetic testing.
• The only gene in which pathogenic variants are known to cause DEB is COL7A1.
• If molecular genetic testing is not diagnostic, examination of a skin biopsy with direct immunofluorescence (IF) for specific cutaneous markers and/or electron microscopy (EM) may be necessary for diagnosis.[1].

Treatment

• There is currently no cure for all types of dystrophic epidermolysis bullosa (DEB).
• Treatment generally focuses on managing signs and symptoms.
• For some individuals, such as those that have a mild form of dominant dystrophic epidermolysis bullosa (DDEB), dystrophic nails may be the only manifestation.
• However, other individuals may have much more severe problems that need to be managed.
• Management typically focuses on treating blisters and avoiding or treating infections.
• Wound care usually included treatment of new blisters by lancing and draining.
• Additionally in most cases, wounds are then dressed with a non-adherent material, covered with padding for stability and protection, and secured with an elastic wrap for integrity.
• Due to the increased risk of bacterial resistance, topical antibiotic ointments and antimicrobial dressings should be reserved for those wounds that are colonized with bacteria and fail to heal, referred to as “critical colonization."
• Individuals with epidermolysis bullosa (EB) have increased caloric and protein needs due to the increased energy utilized in wound healing.
• Involvement of the digestive system in some forms of EB may limit nutritional intake.
• Infants and children with more severe forms of EB and failure to thrive usually require attention to fluid and electrolyte balance and may require nutritional support, including a gastrotomy feeding tube.
• Anemia is typically treated with iron supplements and transfusions as needed.
• Other nutritional supplements may include calcium, vitamin D, selenium, carnitine, and zinc.
• Surveillance is important for individuals with DEB.
• Biopsies of abnormal-appearing wounds that do not heal may be recommended in some types of DEB due to predisposition to squamous cell carcinoma, beginning in the second decade of life.
• Screening for deficiencies of iron, zinc, vitamin D, selenium, and carnitine is typically recommended after the first year of life.
• Routine echocardiograms are recommended to identify dilated cardiomyopathy, and bone mineral density studies are recommended to identify osteoporosis. Activities and bandages that may traumatize the skin (including all adhesives) should typically be avoided.
• Recent treatment advancements and therapies under investigation include but are not limited to

Use of biological dressings to treat chronic or recurrent skin ulcersː

• Bone marrow transplantation
• Intra-dermal (in the skin) injection of fibroblasts
• Protein replacement therapy (intra-dermal injection of type VII collagen)
• Gene therapy
• Revertant mosaicism
• Gene correction technologies (ex. CRISPR)

NIH genetic and rare disease info

• NIH info on Dominant dystrophic epidermolysis bullosa

Dominant dystrophic epidermolysis bullosa is a rare disease.

Dominant dystrophic epidermolysis bullosa Resources
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