Autosomal dominant generalized dystrophic epidermolysis bullosa (ORPHA:231568)
A rare dystrophic epidermolysis bullosa (DEB) characterized by generalized blistering, milia formation, atrophic scarring, and dystrophic nails.
Epidemiology
The prevalence worldwide is unknown, in the USA prevalence at birth is estimated at 1/5,000,000.
Clinical description
The clinical picture of intermediate dominant dystrophic epidermolysis bullosa (DDEB-intermediate) is generally milder than that of the autosomal recessive generalized DEB forms. DDEB-intermediate manifests usually at birth with the development of blisters, primarily affecting the limbs. Blisters heal by developing numerous milia and atrophic scars with an onion-like appearance, particularly visible on the elbows, knees, and hands. Nail dystrophy, always present, can lead to loss of nail plates. Usually, fingers and toes are not affected by major cicatricial retractions. Blisters can develop in the mucosa, mainly in the oral cavity and, less commonly, in the esophagus, where they can cause strictures, often in sharp contrast with the scarce cutaneous involvement. Dental caries are relatively frequent. Corneal and genitourinary tract involvement, anemia, and growth delay are rare.
Etiology
DDEB-intermediate is caused by mutations in the collagen VII gene (COL7A1; 3p21.31) that lead to an alteration of function or a reduction in the amount of collagen VII. The molecular defect impairs collagen VII assembly into anchoring fibrils which fix the basement membrane to the underlying dermis, causing reduced skin resistance to minor trauma.
Diagnostic methods
Diagnosis is suspected at clinical examination and is confirmed by immunofluorescence antigen mapping and/or transmission electron microscopy on skin samples showing a cleavage plane located below the lamina densa of the cutaneous basement membrane zone. Genetic testing confirms the diagnosis.
Differential diagnosis
The differential diagnosis includes other forms of EB. In the neonatal period, aplasia cutis congenita, herpes simplex infection, congenital erosive and vesicular dermatosis, epidermolytic ichthyosis, linear IgA bullous dermatosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis, bullous impetigo, and staphylococcal scalded skin syndrome may need to be considered.
Antenatal diagnosis
Antenatal diagnosis is usually not recommended, but some people who are themselves affected, may request it.
Genetic counseling
Genetic counseling should be offered to all the patients and their parents. The disorder is autosomal dominant and therefore, for each pregnancy there is 50% risk of transmitting the pathogenic variant from an affected individual to offspring.
Management and treatment
Management is preventive: protective padding of the skin and appropriate lifestyle measures reduce blistering, and careful wound care prevents secondary infection and reduces scarring. Oral hygiene is important for the management of caries. When present, esophageal strictures can be treated by balloon dilatation with fluoroscopic guidance. In a minority of patients, a follow-up by a dietitian can be required to evaluate nutritional requirements.
Prognosis
Life expectancy is normal.

                            Last update: 
                            May 2021


                            - Expert reviewer(s): 
                            Dr Michela BRENA | ERN-Skin* - Dr Sophie GUEZ | ERN-Skin* - Dr Gianluca TADINI | ERN-Skin*


                                * European Reference Network