Pseudoxanthoma Elasticum With Generalized Retinal Dysfunction, a Common Finding?

Abstract

Purpose: : Pseudoxanthoma elasticum (PXE [MIM# 264800]) is an autosomal recessive systemic disorder characterized by progressive degeneration and calcification of elastic fibers in connective tissue. The phenotype is variable and includes cutaneous, vascular and ophthalmic abnormalities. The disorder is consequent upon mutations in the ABCC6 gene. Visual impairment is mainly due to neovascular complications and retinal function is usually assumed to be normal or moderately affected. We report here 4 unrelated patients with PXE and generalized retinal dysfunction.

Methods: : Four unrelated patients carrying a clinical diagnosis of PXE presented with unexplained visual loss. After ophthalmologic examination, retinal and macular function was assessed by full field electroretinogram (ERG) and pattern ERG respectively, according to ISCEV recommendations. Molecular analysis of the ABCC6 gene was performed in 3 patients using dHPLC (denaturing High Performance Liquid Chromatography) and direct sequencing.

Results: : Full–field ERG revealed significant reduction of cone and rod responses in all four patients with three functional phenotypes: cone–rod dystrophy (case 1), rod–cone dystrophy (cases 3 and 4) and severe photoreceptor dystrophy involving rods and cones equally (case 2). Funduscopic appearances varied. Diffuse changes extending beyond the arcades were seen (case 1 and 2), and intraretinal crystals (case 1). In case 1, a novel nonsense mutation (p.L1474X) was detected in exon 31 paired with a known frameshift mutation. Mutation analysis in cases 3 and 4 revealed previously reported ABCC6 mutations including one allele with the multi–exon deletion (exons 23–29).

Conclusions: : These findings suggest that generalized retinal dysfunction in PXE might not be uncommon. The mechanism underlying the dysfunction is unknown but might result from metabolic disturbance leading to retinal toxicity. The mutations detected were not dissimilar to those seen previously in PXE and suggest a deficiency of ABCC6; it is likely that the extent of generalized retinal dysfunction is determined by modifying genetic or environmental factors rather than specific ABCC6 mutations.

Keywords: retina • electroretinography: clinical • genetics