Biallelic RDH11 variants cause syndromic retinitis pigmentosa with early-onset cataracts and neurodevelopmental delay: a multicenter case series.

RDH11

Biallelic loss of function of RDH11, a retinol dehydrogenase involved in the visual cycle and systemic retinoid homeostasis

Biallelic RDH11 variants, affecting a retinol dehydrogenase of the visual cycle, were first implicated in a rare condition combining retinal dystrophy, early-onset cataract, neurodevelopmental anomalies and myopathy, initially through single-family reports and more recently in a larger study. Here the authors report a multicentre cohort of eight individuals from seven unrelated families, all carrying homozygous variants including two novel ones, strongly supporting loss of function as the primary disease mechanism. Detailed phenotyping defines a consistent and severe multisystem disorder: bilateral congenital or early-childhood cataracts requiring surgery, together with retinitis pigmentosa. Extra-ocular involvement frequently included neurodevelopmental delay — intellectual disability, autism spectrum disorder, learning difficulties — often with congenital microcephaly, intrauterine and postnatal growth restriction, facial dysmorphism and dental anomalies.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Seven independent families are enough to move RDH11 from candidate to established gene for syndromic retinitis pigmentosa, which is the real contribution of this series. In practice, the combination of bilateral congenital cataract and developmental delay should prompt a search for biallelic RDH11 variants at first exome analysis, without waiting for retinitis to appear. The absence of functional work remains the limitation, but consistent homozygosity across seven independent families largely offsets it.

Analysis by Dr Thibaut Benquey