17 Pellerin, David Danzi, Matt C Renaud, Mathilde Houlden, Henry Synofzik, Matthis Zuchner, Stephan Brais, Bernard AG Gasser Clinical and translational medicine Clinical and translational medicine Wiley Hoboken, NJ 2001-1326 10.1002/ctm2.1504 English e1504 1 14 Hereditary ataxias, especially when presenting sporadically in adulthood, present a particular diagnostic challenge owing to their great clinical and genetic heterogeneity. Currently, up to 75% of such patients remain without a genetic diagnosis. In an era of emerging disease-modifying gene-stratified therapies, the identification of causative alleles has become increasingly important. Over the past few years, the implementation of advanced bioinformatics tools and long-read sequencing has allowed the identification of a number of novel repeat expansion disorders, such as the recently described spinocerebellar ataxia 27B (SCA27B) caused by a (GAA)•(TTC) repeat expansion in intron 1 of the fibroblast growth factor 14 (FGF14) gene. SCA27B is rapidly gaining recognition as one of the most common forms of adult-onset hereditary ataxia, with several studies showing that it accounts for a substantial number (9-61%) of previously undiagnosed cases from different cohorts. First natural history studies and multiple reports have already outlined the progression and core phenotype of this novel disease, which consists of a late-onset slowly progressive pan-cerebellar syndrome that is frequently associated with cerebellar oculomotor signs, such as downbeat nystagmus, and episodic symptoms. Furthermore, preliminary studies in patients with SCA27B have shown promising symptomatic benefits of 4-aminopyridine, an already marketed drug. This review describes the current knowledge of the genetic and molecular basis, epidemiology, clinical features and prospective treatment strategies in SCA27B. PUB:(DE-HGF)16, Review Article; 0, ; Adult Humans Spinocerebellar Ataxias: diagnosis Spinocerebellar Ataxias: drug therapy Spinocerebellar Ataxias: genetics Ataxia: complications Phenotype 4-aminopyridine FGF14 GAA-FGF14 ataxia cerebellar ataxia genetics repeat expansion disorder therapy Journal Article (Review Article) 2024 DZNE-2024-00107 2024 pmc:PMC10819088 pmid:38279833 https://pub.dzne.de/record/267343 https://doi.org/10.1002/ctm2.1504