To assess the diagnostic yield of genetic testing and highlight our experience at our recently established multidisciplinary ataxia clinic.

From 2021-2024, we enrolled 80 adults with clinical signs strongly suggestive of hereditary ataxia but without a genetic diagnosis into our IRB-approved study. Samples were collected for DNA analysis, with repeat expansion panel performed first followed by targeted and/or whole exome sequencing if prior workup was unrevealing. Patients were offered neurologic physical therapy targeted towards patients with ataxia.

Our cohort included 42 men and 38 women (average age 63, range 23-89). After genetic testing through our protocol, 40 patients (50%) had confirmed genetic diagnoses: 14 with cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS), 8 with spinocerebellar ataxia 27B (SCA27B), 4 with SCA6, 3 with SCA8 and 11 with other subtypes of ataxia. 37 patients (46.2%) remained without a genetic diagnosis. Three patients (3.8%) were subsequently determined to have non-genetic causes (1 with MSA-C, 2 with ataxia secondary to vascular insult). Patients were offered medical therapy based on symptoms and/or genetic diagnoses. Notably, of the 8 patients diagnosed with SCA27B, 7 (87.5%) reported symptomatic improvement with dalfampridine. Forty-nine patients (61.3%) attended at least one session of neurologic physical therapy at our institution.

Significant progress has been made particularly with the recent discoveries of CANVAS and SCA27B. Further work involves quantifying response to pharmacotherapy and physical therapy across different genetic subtypes. Establishing a genetic diagnosis can enhance the multidisciplinary clinic experience by customizing treatment plans to align with specific patient needs, ultimately translating to better care.