Abnormal eye movements and photophobia in 2 siblings: achromatopsia type 2 due to mutation of the CNGA3 gene

Mutations of the CNGA3 gene have been associated with autosomal-recessive achromatopsia type 2. Objective: To report 2 siblings (brother and sister) with autosomal-recessive achromatopsia type 2 and a point mutation of the CNGA3 gene. Case report: Setting: A pediatric department in a tertiary general hospital. 8 years old, the brother an 8-year-old male, was admitted almost 3 years ago due to abnormal eye movements which were first noted in infancy. The neurological examination demonstrated horizontal nystagmus in all positions, occasionally vertical nystagmus and striking photophobia exclusively during the day and in the plain daylight. His 14-year-old sister, had demonstrated similar symptoms from infancy, which became less evident throughout the years. Visual evoked potentials and non-corneal electroretinigram were moderate abnormal with prolonged cortical latency P100 and N1, respectively. Fundoscopy was normal, visual acuity was found to be 1/20 bilaterally, while a complete achromatopsia could also be demonstrated in both children. An analysis of CNGA3 and CNGB3 for common mutations revealed the presence of a homozygous point mutation c.754G>A in the CNGA3 gene in both children, while their unaffected parents were found to be heterozygous for the same mutation, thus, establishing the diagnosis of an achromatopsia type 2. Both children keep wearing dark glasses during the day and continue to have significant difficulties in all day tasks. Neurologically they are entirely normal with an IQ within the normal range. Conclusion: These 2 familial cases illustrate the typical clinical phenotype of achromatopsia type 2. The abnormal eye movements may well raise the suspicion of a CNS lesion (i.e. cerebellar dysplasia), a metabolic (i.e. mitochondriopathy) or even a remote neoplastic disorder (i.e. neuroblastoma); however, the typical constellation of nystagmus from early infancy, photophobia and achromatopsia should lead to the correct diagnosis and subsequently to specific molecular testing, thus avoiding unnecessary examinations.