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MED27-related neurodevelopmental disorder is an autosomal recessive condition characterized by global developmental delay, cognitive impairment, limb spasticity, cataracts, and cerebellar hypoplasia. To date, two pedigrees have been reported: a single patient with a homozygous c.74G>A (p.Arg25His) variant (PMID:39296199) and a consanguineous family with two affected siblings harboring c.839C>T (p.Pro280Leu) (one additional affected relative) (PMID:35876425). In vitro functional studies of Arg25His demonstrated significantly reduced MED27 protein expression and weakened MED27–MED14 interaction (PMID:39296199). No conflicting reports have been described. These data support a Limited clinical validity classification for MED27 in NEDSCAC.
Key Take-home: MED27 sequencing should be considered in patients with early-onset developmental delay, spasticity, cataracts, and cerebellar hypoplasia.
Gene–Disease AssociationLimitedTwo pedigrees (one singleton, one sib pair), minimal segregation beyond sibs, concordant functional data Genetic EvidenceLimitedHomozygous missense variants in two families with AR inheritance and segregation in one sib pair Functional EvidenceModerateIn vitro assays show reduced MED27 protein and disrupted MED27–MED14 interaction |