IMMUNOHISTOCHEMICAL, ULTRASTRUCTURAL, AND MOLECULAR-FEATURES OF KINDLER-SYNDROME DISTINGUISH IT FROM DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Background: Kindler syndrome is a rare, inherited skin disease charact erized by acral bullae formation, fusion of fingers and toes, and gene ralized progressive poikiloderma. The purpose of this study was to cla rify the nature of the bullous component of Kindler syndrome and to de termine whether this inherited skin disorder represents a variant of d ystrophic epidermolysis bullosa or a unique independent clinical entit y. Observations: Two unrelated patients with Kindler syndrome were stu died. Electron microscopy demonstrated marked duplication of the lamin a densa, and clefts were observed in areas where the lamina densa was destroyed or obscured. Hemidesmosomes and anchoring fibrils showed nor mal features. Indirect immunofluorescence revealed normal linear label ing with antibodies against hemidesmosomal components (alpha 6 and bet a 4 integrins, BPAG1, and BPAGZ) and against anchoring filament compon ents such as uncein, as detected by the 19-DEJ-1 monoclonal antibody. However, antibodies against the 3 respective laminin 5 chains, type IV collagen, and various type VII collagen epitopes (the aminoterminal N Cl domain, the central triple helical collagenous domain, and the carb oxyterminal end of the triple helical collagenous domain) revealed a b road reticular staining pattern. Molecular screening of the type VII c ollagen gene (COL7A1) in the patients and their parents by heteroduple x analysis failed to detect any bandshifts indicative of pathologic mu tations. Conclusions: These results suggest that the bullous component of Kindler syndrome is distinct from dystrophic epidermolysis bullosa caused by mutations in the type VII collagen gene. Additionally, the differential distribution patterns of uncein and laminin 5 in the pati ents' skin samples support the hypothesis that uncein and laminin 5 ar e different molecules.