Clinical Findings in a Multigeneration Family With Autosomal Dominant Central Areolar Choroidal Dystrophy Associated With an Arg195Leu Mutation in the Peripherin/RDS Gene

Abstract

To characterize clinical findings associated with a mutation in codon 195 (Arg195Leu) of the peripherin/RDS gene in a large multigeneration family of European decent. Methods: Sixteen members from 2 generations underwent ophthalmologic examination, including bestcorrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. All affected family members underwent Farnsworth Panel-D15 color testing. Five selected family members with early stages of the disease underwent multifocal electroretinography. Full-field electroretinography was performed in 2 family members with more advanced fundus changes. Finally, former patients' records and fundus images were analyzed to determine the course of the disease in affected individuals. Results: Nine family members in 2 generations were diagnosed as having autosomal dominant central areolar choroidal dystrophy. The family demonstrated an agedependent increase of central granular fundus abnormalities with progressive development of geographic atrophy. Interindividual phenotypic variability was apparent and ranged from predominantly drusenlike depositions to single perifoveal pigment clumps. Age of onset of visual disturbances varied between 27 and 48 years. All individuals who manifested signs of disease were found to carry an Arg195Leu mutation in the peripherin/RDS gene. Conclusions: Age of onset, progression of the disease, and characteristic fundus abnormalities share similarities to previous reports on families with central areolar choroidal dystrophy associated with peripherin/RDS gene mutations in codons 172, 142, and 195, respectively. However, striking variability in individual phenotypic findings and age of onset in our family suggests that additional factors that modify the defined peripherin/RDS gene mutation Arg195Leu likely influence the severity of the disease. Clinical Relevance: Caution should be advised in predicting the clinical course and severity of the disease based solely on a specific mutation in the peripherin/RDS gene.

PRPH2-Related Retinal Diseases: Broadening the Clinical Spectrum and Describing a New Mutation

“…This is a founder mutation that probably explains in part the high prevalence of mutations in the PRPH2 gene found in a Spanish cohort of autosomal-dominant central retinal dystrophies [ 33 ]. The mutation was first described to cause CACD [ 16 ], but soon after, a more widespread phenotype was described similar to what we found [ 34 ]. A limited phenotype variation was observed in this family, as most but not all members presented with ECA and those presenting CACD belonged mostly to the same branch of the family.…”

Pediatric Hereditary Macular Degenerations

“…Central areolar choroidal atrophy. This is a late onset disease pattern with an atrophic macula [189,190]. There are no flecks and the dark choroid sign is absent.…”

Macular Dystrophies

“…177,[196][197][198][199][200][201][202][203][204] Thus, the choroidal changes are secondary to a genetic abnormality expressed at the level of the photoreceptors, and a more accurate term might be "central areolar retinochoroidal dystrophy (CARCD)." However, numerous reports also link this macular pattern to mutations in PRPH2.…”