Advanced Presentation of GEMIN5 Neurodevelopmental Disorder in an Elderly Female

GEMIN5, an RNA-binding protein, recognizes small nuclear RNAs and delivers them to the survival motor neuron complex for assembly of small nuclear ribonucleoproteins, which is vital for the maintenance of motor neurons. Loss-of-function mutations in the GEMIN5 gene are associated with neurodevelopmental disorders. Biallelic GEMIN5 variants cause motor-predominant developmental delay and cerebellar atrophy. Clinically, GEMIN5 variants have been associated with neurodevelopmental disorder with cerebellar atrophy and motor dysfunction syndrome, which is characterized by developmental and cognitive delay, ataxia, motor dysfunction, hypotonia in infancy, and cerebellar atrophy. We report the case of a 79-year-old woman who presented with progressive ataxia, spastic paraparesis, contractures, bulbar dysfunction, and dementia on a background of learning difficulties. Two pathogenic variants in the GEMIN5 gene were identified by whole-genome sequencing following MRI findings of striking frontotemporal atrophy in addition to cerebellar atrophy.