Clinical and histopathological characteristics of a family with R1141X mutation of pseudoxanthoma elasticum - presymptomatic testing and lack of carrier phenotypes.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder affecting cutaneous, ocular, and cardiovascular systems, caused by mutations in the ABCC6 gene. PXE presents with a marked clinical and genetic heterogeneity. Furthermore, heterozygous carriers may present with limited histopathological features. This study was conducted to investigate a patient with PXE and her family members clinically, histopathologically, and genetically. METHODS: Clinical and histopathological examinations and mutation analyses of ABCC6 gene were performed. RESULTS: Lesional skin biopsy of the patient with PXE demonstrated clumping and fragmentation of elastic fibers, and calcification in the dermis. Non-lesional axillary skin samples of the husband, daughter, and older son were histopathologically normal. The skin from a similar region of a younger son revealed elastic fibers with some fragmentation and clumping but no mineralization. The patient with PXE was homozygous for the R1141X mutation in the ABCC6 gene. The husband had wild-type alleles, while all children were heterozygous carriers. Daily treatment of antioxidant therapy with tocopherol acetate and ascorbic acid was prescribed to the patient with PXE. After one year, both clinical and histopathological regression of the lesions was observed; however, lesions began to progress during the additional 6-month period of treatment. CONCLUSION: The mutation analyses of ABCC6 gene are important to determine the genotype of both patients with PXE and putative heterozygous carriers, as histopathological features of carriers may differ even in the same family. The role of antioxidant therapy for PXE is unclear, and there is a need for controlled clinical trials