Purpose: Retinol binding protein (RBP4) is important for transport of vitamin A from liver to end organs. Variants in the RBP4 gene have been associated with a broad range of ocular phenotypes but only in a small number of patients.
Methods: We describe the phenotypes in a multi-generation family with RPB4 variants.
Results: A sibling pair was found to be homozygous for a novel pathogenic variant (c.112-2A>G) in RBP4. Both had presented with early-onset atypical retinitis pigmentosa and they had rheumatoid arthritis and acne. The female sibling became the mother of a child, heterozygote for the variant. The child was born with ocular malformations including corneal opacities, microcornea, posterior staphyloma including the optic nerves. The child did not demonstrate any signs of night blindness or progressive retinal dystrophy. In addition, two older family members were reported to be night blind and two distant relatives were born with spina bifida but were not available for genetic testing.
Discussion: Homozygous variants were associated with severe retinal dystrophy, rheumatoid disease, and acne whereas malformations were likely associated with reduced intra-uterine vitamin A levels. It seems advisable to monitor and treat vitamin A deficiency in all patients carrying one or more variants in the RBP4 gene especially during pregnancy.
Keywords: RBP4 gene; congenital eye malformations; retinal dystrophy; staphyloma.