The Phenotype of Lca Patients With Mutations in Cep290

Abstract

Purpose: : To study the phenotype in Leber congenital amaurosis (LCA) patients carrying homozygous or compound heterozygous CEP290 mutations and to establish a genotype-phenotype correlation.

Methods: : More than 20 LCA patients with proven mutations in CEP290 were identified for phenotyping purposes. Clinical data were analysed retrospectively and all patients underwent ophthalmic examintation, including visual acuity (VA), refraction, slit lamp examination and funduscopy. To investigate subclinical features of Joubert syndrome we performed neuro-imaging (CT, MRI) and ultrasonography of the kidneys.

Results: : Visual acuity ranged from light perception negative to counting fingers. All patients were high hypermetropes (ranging from +8.00 to +18.50). Anterior segment exams ranged from normal to full ecstatic corneas. Funduscopy ranged from essentially normal in childhood to subtle abnormalities in the posterior pole and periphery with aging. One patient developed Coat’s-like exudative vasculopathy. Neuroimaging and ultrasonography of the kidneys did not reveal any abnormalities. Joubert syndrome was excluded in all patients even though three patients had learning difficulties and difficulties with proprioception.

Conclusions: : Pathogenic mutations in the CEP290 gene lead to a clinically severe form of LCA with mild funduscopic abnormalities. The CEP290 phenotype seems distinguishable from other types of LCA.

Keywords: genetics • retinal degenerations: hereditary