Autosomal-recessive cerebellar ataxias

The autosomal-recessive cerebellar ataxias comprise more than half of the known genetic forms of ataxia and represent an extensive group of clinically heterogeneous disorders that can occur at any age but whose onset is typically prior to adulthood. In addition to ataxia, patients often present with polyneuropathy and clinical symptoms outside the nervous system. The most common of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene, but recent advances in genetic analysis have greatly broadened the ever-expanding number of causative genes to over 50. In this review, the clinical neurogenetics of the recessive cerebellar ataxias will be discussed, including updates on recently identified novel ataxia genes, advancements in unraveling disease-specific molecular pathogenesis leading to ataxia, potential treatments under development, technologic improvements in diagnostic testing such as clinical exome sequencing, and what the future holds for clinicians and geneticists.