Epidermolysis Bullosa With Congenital Localized Absence Of Skin And Deformity Of Nails

A number sign (#) is used with this entry because of evidence that the disorder results from mutation in the COL7A1 gene (120120) and is therefore a clinical variant of dominant dystrophic epidermolysis bullosa; see 120120.0008.

Bart et al. (1966) reported a family with a syndrome consisting of congenital absence of skin on the lower extremities, blistering of skin and mucous membranes, and congenital absence or deformity of nails. Twenty-six persons were affected, and penetrance was complete. The condition seemed distinct from previously reported forms of local aplasia of skin and from various other types of epidermolysis bullosa. Congenital localized absence of skin is probably an occasional manifestation of epidermolysis bullosa, the result of in utero blistering (Bart, 1970). Father-son transmission was noted. A similar family was reported from the Faroe Islands by Joensen (1973). Skoven and Drzewiecki (1979) reported a possible sporadic case.

Kanzler et al. (1992) described a family in which persons in 4 generations had epidermolysis bullosa simplex with congenital localized absence of skin (CLAS). The proband was admitted to hospital at 1 week of age with hypernatremic dehydration. At birth a large area of denuded skin was present on the right leg as well as a smaller area on the dorsal aspect of the left wrist and hand. The areas of CLAS healed completely by 3 months of age with minimal scarring. Nails were normal at birth. The proband's mother had an identical lesion on her leg at birth that resulted in a barely perceptible scar. She displayed no nail changes but did have skin fragility. Kanzler et al. (1992) suggested that the family reported by Bart et al. (1966) probably had generalized EB simplex of the Koebner type (131900). They pointed out that CLAS has been reported in association with all 4 major types of inherited epidermolysis bullosa. They suggested that the areas of localized absence of skin are a clinical manifestation of EB in utero and not a separate entity such as aplasia cutis congenita (107600).

In some families with Bart syndrome, linkage to the gene for type VII collagen (120120) has been demonstrated (Gruis et al., 1992), suggesting that this is the site of the mutation in some and perhaps all cases.

Descriptions of patients with clinical findings similar to those in the large family reported by Bart et al. (1966) suggested that the Bart syndrome may represent any of the 3 subtypes of epidermolysis bullosa: epidermal, junctional, or dermal. Because no histologic or ultrastructural studies were done in Bart's kindred, and neither immunohistologic nor genetic linkage methods were available at the time, classification of the syndrome remained unclear. Zelickson et al. (1995) reported the findings of clinical, ultrastructural, immunohistologic, and genetic linkage studies of the original kindred and their descendants. The clinical findings were similar to those reported in 1966. They did, however, detect persistence of blistering into adult life and mild atrophic scarring and milia formation at sites of blistering in some family members, a finding not noted in the original study. Hypertrophic scarring and albopapuloid lesions were not detected. Ultrastructural analysis of skin from affected family members showed poorly formed anchoring fibrils and cleavage below the lamina densa. Immunohistochemical staining localized type IV collagen at the roof of blistered skin. Staining for type VII collagen was found to have a normal distribution in nonblistered skin. Genetic linkage studies mapped the gene for the disease in this family to 3p at or near the site of the gene encoding type VII collagen. Christiano et al. (1996) demonstrated a specific mutation in the COL7A1 gene in this family (120120.0008).