Clinical heterogeneity between two Japanese siblings with congenital achromatopsia

Congenital achromatopsia is a stationary retinal disorder with autosomal recessive inheritance. It is characterized by significant attenuation of cone-photoreceptor function. Symptoms include photophobia, nystagmus, and poor visual acuity from birth. Unlike in cone or cone-rod dystrophies, the retinal fundus usually appears normal. Here we describe two siblings with congenital achromatopsia, who exhibit different ophthalmic phenotypes. History was taken, and ophthalmic examinations were performed in a 7-year-old girl and her 5-year-old brother, who were referred to our department because of poor visual acuity. Two of their grandparents were brother and sister, suggesting an autosomal recessive transmission in inheritance. They have been followed for more than 13 years since the initial evaluation. Symptoms, visual acuity, and kinetic visual field were very similar to each other, consistent with findings of typical congenital achromatopsia. However, color-vision tests suggested that the brother had residual color discrimination, but the sister did not. The siblings had different full-field electroretinographic and spectral-sensitivity findings: residual cone functions were detected in only the brother, in agreement with his residual color vision. They also had different findings of retinal fundi and ocular refractions: the sister had bilaterally atrophic-appearing macular lesions and myopic errors. In contrast, the brother remains hyperopia and has exhibited no specific retinal findings until age 18 years. The causes why both complete and incomplete achromats occur in the siblings are uncertain but might be caused by modifying effects of sex-related genes or by environmental factors influencing certain gene regulations in cone photoreceptors.