[Linear Darier disease in two siblings. An example of loss of heterozygosity]

Darier's disease or keratosis follicularis is an autosomal dominant acantholytic disorder that frequently arises as a result of spontaneous mutation. It is either a generalized or localized condition due to a mutation in the SERCA2 12q23-q24,1 resulting in a faulty organization of the tonofilaments. We present two siblings affected with the linear form of this disorder and discuss these cases as an example of the genetic mechanism of loss of heterozygosity.

A 7 year-old girl was referred for evaluation of linear lesions present since the first year of age. Examination disclosed red, 1 to 2 mm papules that coalesced to form linear plaques on the left side of the vulvar and perianal areas, and on the left hand and foot. Her older brother had similar lesions in a linear arrangement on the left side of the face neck and homolateral foot. No lesions were found in their parents. Biopsies of both affected children revealed an intraepidermal suprabasal cleft. Dyskeratotic cells were present in the spinous layer, and corps ronds and grains near the granular layer.

The linear form of Darier's disease could result from genetic mosaicism for this autosomal dominant disorder. As these children have a more pronounced involvement than the usual Darier's disease lesions, disposed in a linear arrangement, they probably represent a type 2 segmental manifestation of the disorder. Likewise, the presence of the same linear disorder in two siblings could be explained by loss of heterozygosity for the Darier's disease gene.