Pseudoxanthoma elasticum: Wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6

Purpose: Pseudoxanthoma elasticum is an autosomal recessive disorder of elastic tissue in the skin, eyes, and cardiovascular system, caused by mutations in the ABCC6 gene. The purpose of this study was to check variability in expression within one genotype and look for pseudoxanthoma elasticum signs in heterozygotes. Methods: We examined a relatively large, in comparison with the present literature, group of adult persons homozygous or heterozygous for the c.3775delT mutation in the ABCC6 gene, front a genetically isolated population in the Netherlands. All participants filled out a questionnaire and underwent standardized dermatologic and ophthalmologic examinations with photography of skin and fundus abnormalities. Skin biopsies from affected skin or a predilection site and/or a scar were examined and compared with biopsies from controls. Results: Skin abnormalities, ophthalmologic signs, and cardiovascular problems varied greatly among the 15 homozygous participants. There was no correlation among severity of skin, eyes, or cardiovascular abnormalities. None of the 44 heterozygous participants had any sign of pseudoxanthoma elasticum on dermatologic, histopathologic, and/or ophthalmologic examination, but 32% had cardiovascular disease. Conclusion: Individuals homozygous for the c.3775delT mutation can have a highly variable phenotype. We did not find pseudoxanthoma elasticum eye or skin abnormalities in the heterozygous family members. Genet Med 2009:11(12):852-858