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Dystrophic Epidermolysis Bullosa.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2006 Aug 21 [updated 2015 Feb 26].

Author information

1
Director, EBDx Program, GeneDx, Inc, Gaithersburg, Maryland
2
Medical Director, Cincinnati Children's Epidermolysis Bullosa Center, Cincinnati Children's Hospital, Cincinnati, Ohio

Excerpt

CLINICAL CHARACTERISTICS:

Dystrophic epidermolysis bullosa (DEB) comprises two types based on inheritance pattern: Recessive DEB, including severe generalized (RDEB-sev gen; formerly called Hallopeau-Siemens type [RDEB-HS]) and generalized other (RDEB-O; formerly called non-Hallopeau-Siemens type [RDEB-non-HS]). Dominant DEB (DDEB). In RDEB-sev gen, blisters affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, severe nutritional deficiency and secondary problems are common. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, a hallmark of this disorder. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB-O may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the severe, mutilating scarring seen in RDEB-sev gen. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.

DIAGNOSIS/TESTING:

The only gene in which mutation is known to cause DEB is COL7A1. Sequencing of exons 73, 74, and 75 of COL7A1 detects pathogenic variants in 75% of families with DDEB; sequencing of all coding exons detects pathogenic variants in about 95% of individuals with either DDEB or RDEB. In the absence of a confirmatory molecular diagnosis, examination of a skin biopsy by transmission electron microscopy (EM) and/or immunofluorescent (IF) antibody/antigen mapping can help to establish the diagnosis.

MANAGEMENT:

Treatment of manifestations: New blisters should be lanced, drained, and in most cases dressed with a non-adherent material, covered with padding for stability and protection, and secured with an elastic wrap for integrity. Infants and children with RDEB-sev gen and failure to thrive require attention to fluid and electrolyte balance and may require nutritional support, including feeding gastrostomy. Anemia is treated with iron supplements and transfusions as needed. Other nutritional supplements may include calcium, vitamin D, selenium, carnitine, and zinc. Occupational therapy may help prevent hand contractures. Surgical release of fingers often needs to be repeated. Prevention of primary manifestations: Dressings and padding are needed to protect bony prominences from blister-inducing impact; if a fetus is known to be affected with any form of DEB, cesarean delivery may reduce trauma to the skin during delivery. Prevention of secondary complications: The most common secondary complication is infection; treatment of chronic wound infection with both antibiotics and antiseptics is necessary. Surveillance: Beginning in the second decade of life, biopsies of abnormal-appearing wounds that do not heal or have exuberant scar tissue are indicated for evidence of squamous cell carcinoma. Screening for deficiencies of iron, zinc, vitamin D, selenium, and carnitine should start after the first year of life. Routine echocardiograms are recommended to identify dilated cardiomyopathy and bone mineral density studies to identify osteoporosis. Agents/circumstances to avoid: Activities/bandages that traumatize the skin; all adhesives. Evaluation of relatives at risk: Evaluating an at-risk newborn for evidence of blistering is appropriate so that trauma to the skin can be avoided as much as possible. Pregnancy management: Cesarean section is often recommended to avoid vaginal delivery in a fetus at risk.

GENETIC COUNSELING:

Dystrophic epidermolysis bullosa is inherited in either an autosomal dominant (DDEB) or autosomal recessive (RDEB) manner. Molecular characterization of pathogenic variants is the only accurate method to determine mode of inheritance and recurrence risk; phenotype severity and EM/IF findings alone are not sufficient. DDEB. About 70% of individuals diagnosed with DDEB are reported to have an affected parent. If a parent of a proband with DDEB is affected, the risk to the sibs is 50%. Each child of an individual with DDEB has a 50% chance of inheriting the pathogenic variant. RDEB. Each sib of an affected individual whose parents are both carriers has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. If the pathogenic variant(s) have been identified in an affected family member, prenatal testing for pregnancies at increased risk may be available from a clinical laboratory that offers either testing for this disease/gene or custom prenatal testing.

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