Late-Onset Ataxia, Chorea, Cognitive Impairment, and Insomnia: Expanding the Phenotype of IRF2BPL-Related Disease

The interferon regulatory factor 2 binding protein-like (IRF2BP) gene is an intronless gene located on chromosome 14 (14q24.3)and expressed in various human tissues, including the brain.While the exact functions of IRF2BPL are not fully understood, it is believed to play crucial roles in neuronal development, homeostasis, transcriptional regulation, and the ubiquitin-proteasome pathway (1).Autosomal dominant mutations in this gene have been linked to severe neurodevelopmental disorders, typically presenting in early childhood with symptoms such motor regression, and epilepsy (1).Recently, IRF2BPL has also been associated with a late-onset neurodegenerative phenotype (2), (3).We report a case of a 59-year-old patient with an IRF2BPL pathogenic mutation, presenting with progressively worsening ataxia, chorea, dysarthria, and cognitive difficulties, thereby expanding the phenotypic spectrum of IRF2BPL-related disorders. Case ReportA 59-year-old Afro-Caribbean woman with a history of insomnia and depression diagnosed in her 20's presented with an 18-year history of progressively worsening imbalance, abnormal involuntary movements, and cognitive decline.Her symptoms initially began with mild instability and occasional falls but gradually advanced to severe ataxia, double incontinence, and significant cognitive decline, ultimately leading to a high level of dependence on her family for daily activities.No seizures were reported.