Atypical presentation of pattern dystrophy in two families with peripherin/RDS mutations

Abstract

Purpose To describe the atypical clinical presentations of pattern dystrophy (PD) in two unrelated families with novel peripherin/RDS mutations. Design Observational case reports and family genetic study with review of peripherin/RDS mutations. Participants Affected and unaffected members of two families with PD. Methods The probands of two families, as well as other family members, underwent an ophthalmologic assessment including slit-lamp biomicroscopy, applanation tonometry, and a dilated fundus examination. Goldmann visual fields and fluorescein angiography were performed, wherever appropriate. Blood samples were obtained from affected and selected unaffected members of the families for DNA analysis. Results The proband of family 1 had an acute onset of decreased vision and a yellowish lesion in both maculae that appeared inflammatory. However, resolution of the acute lesion ultimately resulted in fundus changes more typical for PD. Moreover, the proband’s sister showed more classic-appearing PD lesions. Screening of the peripherin/RDS gene for sequence variations showed a 2-bp deletion, resulting in a translational frameshift at codon 290 in affected members of the family. The proband’s father, who showed this sequence variation, did not have a macular lesion. The proband of family 2 was asymptomatic and showed a fundus phenotype similar to fundus flavimaculatus. The patient had normal visual acuity and did not demonstrate a “dark choroid” on fluorescein angiography. Molecular screening showed a Gln331stop variation in the peripherin/RDS gene. Conclusions We describe two novel mutations in the peripherin/RDS gene in two unrelated families with PD. Clinicians should recognize the atypical features that may occur in patients with PD. A suspected diagnosis of PD may be confirmed by the identification of a mutation in the peripherin/RDS gene. In isolated family members with PD, a mutation in this gene may occur even in the absence of a clinically discernible macular lesion.