EPOS

European Paediatric Ophthalmological Society

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Does autosomal dominant pseudoxanthoma elasticum exist?

Plomp Astrid, Hu Xiaofeng, Peek Ron, de Jong Paulus, Bergen Arthur
¹The Netherlands Ophthalmic Research Institute

Background: Pseudoxanthoma elasticum (PXE) is a heritable disease of elastic tissue, especially affecting the skin, the eyes and the cardiovascular system. Most familial cases show autosomal recessive (AR) inheritance. In a small subset of families autosomal dominant (AD) inheritance has been reported. Mutations in the ABCC6 gene have been found in sporadic patients, in families with AR as well as in families with putative AD PXE. Purpose: To answer the question "Does autosomal dominant PXE really exist?" Methods: We reviewed the literature on AD PXE and we studied in detail a selection of potentially dominant pedigrees from our data set of 62 PXE patients and families, both clinically and by DNA studies. Individuals were considered to have definite PXE if they had characteristic ophthalmologic and dermatologic signs. Results: In most families with putative AD PXE, definite PXE was present in one generation and only part of the phenotype was present in the other generation(s). In the literature we found only three families with definite PXE in two successive generations, no families with definite PXE in three or more generations. Our own data set comprised three putative AD families. Extensive DNA studies revealed a mutation in only one ABCC6 allele in the patients of those families. Merely one of the families showed definite PXE in two generations. Pseudodominance could not be excluded in this family. Conclusion: We did not find convincing evidence of AD inheritance in PXE. If AD PXE exists, it is rare and probably has low penetrance. Even then, one would expect more reports of definite PXE in two and more successive generations. Part of the phenotype in family members could be due to expression in heterozygous carriers of an AR disease. However, we neither can exclude the existence of AD PXE as yet. More clinical and molecular studies of families with (features of) PXE in two or more generations should shed light on the possible mechanisms.