Objectives: Ocular albinism type 1 (OA1) is an X-linked disorder with an estimated prevalence of 1 in 60,000. Affected males show nystagmus, strabismus, photophobia, iris translucency, retinal hypopigmentation, and foveal hypoplasia. Heterozygous females are asymptomatic but could present iris transillumination and patchy pattern of retinal pigmentation. OA1 is due to mutations of the G-protein-coupled receptor 143 gene (GPR143) encoding a cell receptor involved in melanosomes biogenesis and transport. Phenotype is mainly restricted to eyes, and data on neurodevelopmental outcome are not available. The aim of the study was to explore the visual and neuropsychiatric clinical profile in children with ocular albinism and to examine GPR143 gene to determine which aspects of the clinical picture best characterize ocular albinism due to a GPR143 mutation.
Content: Methods: We reported a series of 13 children (12 males, mean age: 5.6 years) with clinical signs of ocular albinism. All of them underwent an ophthalmological, neurovisual, neuropsychiatric, and cognitive (Griffiths Mental Development Scale/Wechsler Preschool and Primary Scale of Intelligence III) evaluation. Brain magnetic resonance imaging (MRI), electroretinography (ERG), visual evoked potentials (VEP), and GPR143 gene mutation analysis were also performed.
Results: All the 13 patients showed refractive errors, retinal hypopigmentation, and nystagmus (pendular in five cases, jerk in three, and pendular with some jerks in five) which impaired fixation, smooth pursuit, and saccades. Iris translucency was observed in eight patients and foveal hypoplasia in seven. Strabismus was documented in two children. A reduced visual acuity and contrast sensitivity was detected in 11 and 9 cases, respectively. The neuropsychiatric clinical profile and cognitive level were normal in 11 patients; an expressive and pragmatic language impairment was detected in a boy and a cognitive deficit associated with a mixed receptive-expressive language disorder was diagnosed in another one. Brain MRI and ERG were normal in all the patients while VEP was abnormal (latency delay and amplitude decrease) in 10 patients. Mutations in the GPR143 gene were identified in two cases, the same who presented also a neurodevelopmental disorder.
Conclusion: These data seem to underline that when the ocular albinism is caused by mutations in GPR143 gene, it could present a more severe phenotype, characterizing not only by ocular involvement but also by a neurodevelopmental disorder. Our findings enlarge the spectrum of X-linked ocular albinism.
