title: Subdural effusions and lack of early pontocerebellar hypoplasia in siblings with RARS2 mutations.
abstract: Mutations in the recently described RARS2 gene encoding for mitochondrial arginyl-transfer RNA synthetase give rise to a disorder characterised by early onset seizures, progressive microcephaly and developmental delay. The disorder was named pontocerebellar hypoplasia type 6 (PCH6) based on the corresponding radiological findings observed in the original cases. We report two siblings with the RARS2 mutation who displayed typical clinical features of PCH6, but who had distinct neuroimaging features. Early scans showed marked supratentorial, rather than infratentorial, atrophy, and the pons remained preserved throughout. One sibling also had bilateral subdural effusions at presentation. The deceleration in head growth pointed to an evolving genetic/metabolic process giving rise to cerebral atrophy and secondary subdural effusions. RARS2 mutations should be considered in infants presenting with seizures, subdural effusions, decelerating head growth and evidence of cerebral atrophy even in the absence of pontocerebellar hypoplasia on imaging.
authors.affiliation: Department of Paediatric Neurology, Oxford University Hospitals, , Oxford, UK.
authors.forename: Katherina
authors.initials: K
authors.lastname: Kastrissianakis
authors.forename: Geetha
authors.initials: G
authors.lastname: Anand
authors.forename: Gerardine
authors.initials: G
authors.lastname: Quaghebeur
authors.forename: Sue
authors.initials: S
authors.lastname: Price
authors.forename: Prab
authors.initials: P
authors.lastname: Prabhakar
authors.forename: Jasmina
authors.initials: J
authors.lastname: Marinova
authors.forename: Garry
authors.initials: G
authors.lastname: Brown
authors.forename: Tony
authors.initials: T
authors.lastname: McShane
mesh_terms: D001126:Arginine-tRNA Ligase / Q000235:genetics*; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009849:Olivopontocerebellar Atrophies / Q000175:diagnosis / Q000235:genetics*; D011149:Pons / Q000002:abnormalities* / Q000473:pathology; D035781:Siblings; D013353:Subdural Effusion / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D001126:Arginine-tRNA Ligase
keywords: Epilepsy; Microcephaly; Pontocerebellar Hypoplasia Type 6; RARS2; Subdural Effusion