Determine the yield of genetic testing for new patients presenting to a tertiary ataxia clinic over a five-year period.

Cerebellar ataxias are a diverse group of disorders, many of which have genetic etiologies. While advances in genetic testing have expanded the yield of genetic testing, a sizeable number of late-onset cerebellar ataxias remain without an identified genetic cause.

Medical records for new patients presenting to a tertiary ataxia clinic for between January 1, 2016 and January 1, 2021 were reviewed. Data collected included age at presentation, family history of similar symptoms, ataxic features on exam and baseline SARA, and genetic testing results and phenotype correlation. Changes to medical management were tracked for those receiving genetic diagnoses.

Of the 785 patients presenting to ataxia clinic during this time, 106 underwent genetic testing as part of their workup with 100 undergoing testing for common repeat expansions first. A total of 44 (41.5%) of patients received a genetic diagnosis with 32 receiving a diagnosis for repeat expansion associated disorders (32% of those undergoing targeted sequencing) and 12 being diagnosed through ataxia exome sequencing (33% of those undergoing ataxia exome sequencing). Of the 679 patients who did not undergo genetic testing, 10.7% had genetic diagnoses established before referral, 73.9% had diagnoses not requiring genetic testing, and 15.3% had diagnoses not established. Ataxia exome sequencing led to changes in clinical management in 4 patients, cascade diagnostic testing that identified mutations in four additional family members.

Genetic testing resulted in 41.5% of new patients undergoing testing, with exome sequencing expanding the diagnostic yield by identifying a diagnosis in about one in every three patients undergoing testing. However, a significant number of patients remain without a diagnosis.