Title: Dominant, dystrophic epidermolysis bullosa
Authors: Arash K Asadi  and Seth J Orlow
Affiliations: New York University Departent of Dermatology
Citation: Dermatology Online Journal 7(2): 13
Keywords: congenital, childhood

Body:
I: History
This is a 3 month-old-girl who presented with lesions involving the scalp,  face, oral mucosa, trunk, extremities, and genitalia, present since birth. 
A three-month-old girl was born with denuded, crusted erosions along the pretibial skin and dorsal surfaces of her feet, blisters of her skin, and nail dystrophy. As the diagnosis of neonatal sepsis was initially considered, she was transferred to the Neonatal Intensive Care Unit where intravenous antibiotics were administered. The cutaneous blisters spontaneously improved. She has had persistent intraoral erosions, which have not interfered with proper feeding. The patient's parents are non-consanguineous, and there is no history of mucocutaneous abnormalities in any family member, which includes the patient's elder sister.
I: Physical Examination
The patient was a well nourished, well-developed infant with no dysmorphic features. Multiple, small, crusted patches with milia were present on the scalp and less prominently on the face. Areas of normal scalp hair were noted. Multiple patches of mila were present along the axillary areas, the central chest, lower abdomen, right thigh, and the dorsa of the hands and feet. An erosion was noted on the left chest. Erythematous and atrophic but epithelialized patches were present over the lower pretibial surfaces and dorsa of the feet. There was dystrophy and loss of several fingernails and toenails. Erosions were present on the dorsum of the tongue and the left labia majora. 
Figures 1 and 2: 011601-3a.jpg, 011601-3b.jpg

I: Laboratory Data
Analysis of DNA for mutations in collagen 7A1 gene is pending. 
I: Histopathology
There was a detached epidermis with an intact basal-cell layer and a preserved rete-ridge pattern. The dermal portion of the specimen contained a sparse infiltrate of small lymphocytes and rare eosinophils.
I: Diagnosis
Dominant, dystrophic epidermolysis bullosa with congenital localized absence of skin and deformity of nails (Bart's syndrome) 
I: Comment
Bart's syndrome is an autosomal dominant genodermatosis with full penetrance but variable expressivity, in which there is a coexistence of congenital localized absence of the skin and epidermolysis bullosa. The congenital localized absence of skin is confined to regions of the lower extremities distal to the knees. Later, there is mucocutaneous blistering, which, in some instances, results in mild, atrophic scars and milia. The blisters improve but may persist in an attenuated fashion into adulthood. Nail dystrophy or loss is a prominent feature in many patients. 
Ultrastructural studies of Bart's original kindred showed that the disease is associated with blisters at the sublamina densa with abnormal quantity and quality of anchoring fibrils in a pattern similar to that observed in dystrophic epidermolysis bullosa. The basal keratinocytes, tonofilaments, and hemidesmosomes are unaffected. Genetic linkage analysis has shown cosegregation of Bart's syndrome gene locus with COL7A1 gene on chromosome 3p21 in two kindreds. Mutation analysis of the COL7A1 gene of patients from Bart's original kindred showed a G-to-A transition in exon 73, causing a glycine-to-arginine substitution in the triple-helical domain of type VII collagen, which affirms that this kindred suffered from an allelic variant of dominant, dystrophic epidermolysis bullosa. 
Some reports have documented congenital localized absence of skin in association with all major types of epidermolysis bullosa, which suggests that the congenital localized absence of skin may be secondary to blistering of the skin in utero. A recent consensus statement recommended that the term Bart's syndrome be eliminated and that such patients be classified according to their underlying type of epidermolysis bullosa. However, the association of a familial occurrence of congenital localized absence of skin with a specific mutation in COL7A1 suggests that Bart's syndrome may indeed be a unique clinical entity. 

References:
Gruis NA, et al. Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant form of dystrophic epidermolysis bullosa in two Dutch kindreds. J Invest Dermatol 99:528, 1992 
Zelickson B, et al. Bart's syndrome: ultrastructure and genetic linkage. Arch Dermatol 131:663, 1995 
Bart BJ, et al. Congenital localized absence of skin and associated abnormalities resembling epidermolysis bullosa: a new syndrome. Arch Dermatol 93:296, 1996
Christiano AM, et al. Genetic basis of Bart's syndrome: a glycine substitution mutation in the type VII collagen gene. J Invest Dermatol 106: 1340, 1996 
Fine JD. Revised classification system for inherited epidermolysis bullosa: report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa. J Am Acad Dermatol 42:1051, 2000