Phenotypic and Molecular Analysis of RP and LCA Patients With Coats-Like Exudative Vasculopathy Without the RP12 Phenotype

Abstract

Purpose: : Coats-like exudative vasculopathy is a rare complication in patients with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). The association of Coats-like exudative vasculopathy and RP with preserved para-arteriolar retinal pigment epithelium (RP12) caused by mutations in the CRB1 gene has been established. The purpose of this project was to study RP and LCA patients with Coats-like exudative vasculopathy without the RP12 phenotype and to identify the genetic causes.

Methods: : Eight RP patients of 7 families (3 patients of 2 autosomal recessive families, 1 patient of an autosomal dominant family and 4 simplex patients), and 3 isolated LCA patients with uni or bilateral exudative vasculopathy were examined including electroretinography (11 patients), perimetry (10 patients), and fundus photography (10 patients). On 3 patients follow-up of more than 20 years was available. Blood samples were obtained for DNA analyses.

Results: : Four patients presented with atypical RP and four with classic RP. The fundus abnormalities in the LCA patients varied. Age at recent examination ranged from 4 to 64 years (median 34 years). Visual acuity was 20/200 or less in 14 eyes of 11 patients. Complications of the Coats-like exudative vasculopathy included cystoid macula edema (9 eyes), vitreous hemorrhage (1 eye), exudative retinal detachment (3 eyes) and neovascular glaucoma (4 eyes). Two atypical RP patients of 1 family carried compound heterozygous CRB1 mutations. One patient with classic RP was found to have one CRB1 mutation. The dominant RP patient carried a causative mutation in the PRPF8 gene. In one LCA patient, compound heterozygous CEP290 mutations were detected. No novel mutations were identified.

Conclusions: : Coats-like exudative vasculopathy in RP and LCA patients leads to a rapid loss of (residual) visual function. Besides mutations in the CRB1 gene, PRPF8 and CEP290 mutations may be associated with RP and LCA with Coats-like exudative vasculopathy.

Keywords: retinal degenerations: hereditary • genetics