Malformations of cortical development

Gene: RDH11

Green List (high evidence)

Comment on list classification: There are more than 3 unrelated individuals reported with biallelic RDH11 variants and corpus callosum hypoplasia. Hence, this gene should be promoted to Green on Malformations of cortical development at the next update.

Created: 1 Apr 2026, 1:44 p.m. | Last Modified: 1 Apr 2026, 1:44 p.m.

Panel Version: 7.48

PMID: 41904678 Radio et al., 2026
Report of 16 affected individuals from 9 unrelated families with biallelic LoF RDH11 variants, frequently showing juvenile-onset progressive myopathy with vacuolar degeneration and prodromic asymptomatic hyperCKemia. Common features included: neurodevelopmental impairment (16/16), microcephaly (10/16), retinitis pigmentosa (8/16), juvenile-onset cataracts (11/16), myopathy (8/15), progressive night blindness (9/16), hypoplasia of corpus callosum (8/10 assessed by MRI). Microcephaly and distinct craniofacial traits were also recurrent. Short stature was reported in 4/16 patients.
Muscle weakness was reported as slowly progressive, associated with myopathic facies and exercise intolerance with onset in the first or second decade of life.

PMID: 41459630 Stephenson et al., 2025
Report of a visually asymptomatic 7-year-old boy carrying a homozygous null variant in RDH11 [NM_016026.4:c.216C>A:p.(Cys72*)] with autism, dysmorphic features, oligodontia, microcephaly (<3rd centile) and a novel inherited retinal dystrophy. This retinopathy consisted of yellow deposits and hyperpigmentation within the RPE with absent autofluorescence and a normal electroretinogram. No mention of brain imaging.

PMID: 34988992 Liu et al., 2022
15yo Chinese patient with retinitis pigmentosa (RP), juvenile cataracts, intellectual disability, and myopathy. No microcephaly seen, no abnormalities found on MRI. First admitted to the clinic at 7 years old. Trio WES identified variants in RDH11: c.938T>C (p.Leu313Pro) and c.75-3C>A - confirmed in trans. Splice variant shown to cause exon 2 skipping resulting in (p.Lys26Serfs*38) change. Using immunofluorescence, authors found mislocalization of RDH11 protein in muscle cells of the patient.

PMID: 24916380 Xie et al., 2014
3 sibs aged 8-19 years (Italian-American family) with juvenile cataracts (onset at 8-10 years old), issues with night vision, and retinitis pigmentosa, as well as other syndromic features: facial dysmorphologies, psychomotor developmental delays, learning disabilities and short stature. WES detected comp het RDH11 mutations c.C199T:p.R67* and c.C322T:p.R108*. No mention of muscle weakness or microcephaly. No brain imaging done.

RDH11 is putatively associated in OMIM with AR Retinal dystrophy, juvenile cataracts, and short stature syndrome, OMIM:616108 (accessed 1st Apr 2026).
Sources: Literature

Created: 1 Apr 2026, 1:26 p.m. | Last Modified: 1 Apr 2026, 1:43 p.m.

Panel Version: 7.47

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Retinal dystrophy, juvenile cataracts, and short stature syndrome, OMIM:616108; Neurodevelopmental delay, HP:0012758; Juvenile cataract, HP:0001118

Publications

• 24916380
• 34988992
• 41459630
• 41904678