Clinical Features In Patients With Cone-Rod Dystrophy Or Retinitis Pigmentosa Due To Mutations In C8orf37

Abstract

Purpose: : Inherited retinal dystrophies such as retinitis pigmentosa (RP) and cone-rod dystrophy (CRD) are highly heterogeneous, both genetically and clinically. Mutations in 43 genes have been associated with autosomal recessive (ar) RP and CRD. Recently, causative mutations in the C8orf37 gene were identified in patients with RP and CRD. Here, we provide the clinical features of the retinal dystrophies associated with mutations in C8orf37.

Methods: : Homozygous mutations in C8orf37 were found in 4 families, including 9 affected individuals. These patients underwent detailed clinical examination, including medical history, ophthalmologic examination, kinetic perimetry, fundus photography, optical coherence tomography (OCT), auto fluorescence imaging (AF) and electroretinography (ERG).

Results: : In families A and B, respectively 2 and 3 affected individuals showed a classic RP phenotype with night blindness followed by concentric loss of visual field. These RP patients had an age of onset ranging from infancy (family A) to adolescence (family B). Severe visual loss to light perception occurred early in the course of the disease. Ophthalmoscopy revealed macular atrophy, as well as bone spicule pigmentations, attenuated retinal vessels and waxy pallor of the optic disc. ERG examination showed non-recordable cone and rod responses in all affected individuals. OCT and AF showed profound photoreceptor degeneration.In families C and D, each with 2 affected individuals, the diagnosis of CRD was made. The age of onset varied from infancy (family D) to adolescence (family C). The initial symptoms were photophobia and subsequent visual loss to counting fingers. Ophthalmoscopic features included profound macular atrophy. OCT and AF showed macular photoreceptor degeneration. The ERG responses were severely reduced in a cone-rod pattern or were non-recordable. Interestingly, both individuals in family C demonstrated polydactyly.

Conclusions: : Mutations in the C8orf37 gene give rise to an early-onset or adolescent-onset autosomal recessive cone-rod dystrophy or autosomal recessive retinitis pigmentosa phenotype with early severe macular involvement.

Keywords: degenerations/dystrophies • mutations • clinical (human) or epidemiologic studies: natural history