Electron microscopy as a means for carrier detection and genetic counselling in families at risk of tuberous sclerosis.
In otherwise asymptomatic parents of two unrelated children severely affected with tuberous sclerosis (TS), the ultrastructure of hypomelanotic skin lesions was investigated. In the hypomelanotic macules of both mothers of the two families, the population density of melanocytes was normal, melanization, however, was markedly suppressed. Therefore, these macules represent typical "white leaf-shaped macules" characteristic of tuberous sclerosis. Especially by applying the dihydroxyphenylalanine (DOPA) reaction to the ultrastructural level, it was possible to separate the TS-macules from the vitiliginous lesions of one father with a decrease of functional melanocytes as well as from other congenital circumscribed hypomelanoses. Thus electron microscopy in combination with the DOPA reaction may be helpful in recognizing a "forme fruste" of the dominantly inherited tuberous sclerosis (i.e. identification of white leaf-shaped macules) to enable genetic counselling and family planning by marking carriers of the mutant TS gene amongst the relatives of a patient and to exclude a sporadic mutation.
D000328:Adult; D002675:Child, Preschool; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D012306:Risk; D012867:Skin / Q000648:ultrastructure*; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology