Aims: To describe the phenotype of members of a large Caucasian British family affected by autosomal dominant cone-rod dystrophy due to an R838C mutation in the guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cyclase-1 (RETGC-1).
Methods: Retrospective review of 29 patients from four generations of the same family.
Results: Visual symptoms usually commenced in childhood. Only two patients, aged 14 and 25 years, had visual acuity compatible with driving. Of the 12 patients aged over 40 years, eight (66%) had vision of counting fingers or worse and were eligible for blind registration in the UK. Of the 29 patients, 18 (62%) had myopia greater than 5 D in at least one eye. Most had discernible macular changes on biomicroscopy, which varied from subtle RPE change to gross macular atrophy. All patients who underwent computerised perimetry exhibited a central or paracentral scotoma with normal peripheral field of vision. Of the 21 patients who underwent electrodiagnostic testing, all exhibited decreased cone function, but rod function was normal in 12 (57%) patients.
Conclusion: We believe this report highlights the importance of phenotype-genotype correlation in cone and cone-rod dystrophies. Increased understanding of the varying phenotypes associated with different genetic mutations allows appropriate counselling of patients. In addition, the phenotypic characterisation of the natural history of these conditions may prove valuable in the future should therapeutic interventions become available.