Electrophysiologic Assessment and Phenotype-Genotype Correlation in Pseudoxanthoma Elasticum

Abstract

Purpose: : Patients with pseudoxanthoma elasticum (PXE) exhibit characteristic findings at the ocular fundus such as angioid streaks, peau d’orange or salmon spots. Recently, panretinal dysfunction was suggested using fundus autofluorescence and electroretinography (ERG). To detect panretinal functional loss and to perform a correlation with mutations in the ABCC6 gene we performed a comprehensive electrophysiological assessment of a large PXE patient cohort.

Methods: : 17 PXE patients were examined by ERG in accordance with the ISCEV standard. Furthermore, electro-oculography (EOG) was performed in 12 of those patients. The diagnosis of PXE was positively confirmed by mutation analysis of the ABCC6 gene, skin biopsy, and/or characteristic funduscopic pathologies in combination with further systemic manifestations typical for PXE.

Results: : ERG showed reduced scotopic and photopic responses in 11 eyes of 6 patients. In further 16 eyes, there were reduced amplitudes in individual recordings. Only in 7 eyes of 5 patients, photopic and scotopic responses were normal. In one patient being compound heterozygous (c.1987C>T, c.3507-3C>T), ERG signals were completely undetectable in two subsequent measurements. Arden ratio was <1.5 (abnormally low) in 2 patients, 1.5-2.0 (borderline) in 8 patients and >2.0 (normal) in only 1 patient. ABCC6 mutations were found in 12 patients. There was no correlation with electrophysiologic findings.

Conclusions: : The ERG and EOG abnormalities in patients with PXE suggest a diffuse dysfunction of the retina and the pigment epithelium. Histological and sd-OCT studies localized the primary pathology to Bruch’s membrane which may lead to generalized alterations of the pigment epithelium and subsequently of the neurosensory retina.

Keywords: retinal degenerations: hereditary • electroretinography: clinical • genetics