Novel clinical presentation of a CRX rod-cone dystrophy

Abstract

We describe a novel clinical presentation of a CRX rod-cone dystrophy in a single family. Two boys ages 6 and 12 years presented with clinical and optical coherence tomography features suggestive of X-linked retinoschisis, but with optic nerve swelling without increased intracranial pressure. One patient had an electronegative electroretinogram (ERG) and the other had rod-cone dysfunction. Neither had retinoschisin (RS1) gene mutations. Biological mother and sister presented with retinal pigment epithelium (RPE) changes and abnormal cone-rod ERG responses. On further testing, next generation sequencing with array comparative genomic hybridisation showed a deletion in exon 4 of the CRX gene. Cystoid maculopathy in young male children can be difficult to distinguish from RS1-associated schisis. Phenotypic variants within a family must prompt a thorough retinal dystrophy evaluation even with electronegative ERG in the presenting child. This novel phenotype for CRX presents with optic nerve swelling and cystoid maculopathy in men, and RPE changes in women.

Keywords: genetics; macula; ophthalmology; retina.

Figure 1

Genetic pedigree and family history showing an autosomal dominant inheritance pattern. ERG, electroretinogram; y, years.

Figure 2

Proband. Case III:3. At age 6 years. (A) Colour fundus photos, white arrows show blurred optic nerve head margins with negative workup for intracranial hypertension and papillitis, arrow heads show cogwheel pattern macular changes. (B) Fundus autofluorescence, dashed arrows show hyperfluorescent ring, arrow heads hyperfluorescent cogwheel pattern. (C) Optical coherence tomography—note the cystic-like changes in the central macula affecting the outer retina layers resembling retinoschisis.

Figure 3

Brother. Case III:2. At age 12 years. (A) Colour fundus photos, white arrows show blurred margins with negative workup for intracranial hypertension and papillitis, arrow heads show cogwheel pattern macular changes. (B) Fundus autofluorescence, dashed arrows show hyperfluorescent ring, arrow heads hyperfluorescent cogwheel pattern. (C) Optical coherence tomography—note the cystic-like changes in the central macula affecting the outer retina layers resembling retinoschisis.

Figure 4

Sister. Case III:1. At age 15 years. (A) Colour fundus photos, white arrows showing superotemporal retinal pigment epithelium (RPE) changes. (B) Red-free fundus photos, white arrows show RPE changes superotemporal. (C) Fundus autofluorescence, note subtle hyperfluorescent dots superotemporally (black arrow). (D) Normal foveal contour on optical coherence tomography.

Figure 5

Mother. Case II:1. At age 40 years. (A) Colour fundus photos, white arrows showing superotemporal retinal pigment epithelium (RPE) changes. (B) Fundus autofluorescence, note subtle hyperfluorescent dots superotemporally (white arrows) and hyperfluorescent ring around the fovea (black arrows).