Practice Recommendations for Genetic Testing of Ataxias

Over the past decade, significant advances in genetic testing for ataxia have improved diagnostic accuracy, informed clinical trial eligibility, guided treatment decisions, and enabled cascade testing of at-risk relatives. While guidance exists for other neurogenetic conditions, there are no standardized guidelines on genetic counseling and testing for individuals with unexplained ataxia.

We conducted a comprehensive literature review on genetic counseling and testing in ataxia, identifying 7362 articles. After removing 2971 duplicates, 4391 articles were screened by two authors using the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) framework. In areas lacking clear published evidence, we convened a multidisciplinary expert panel with clinical and genetic expertise in ataxia. Following conflict resolution and additional filtering, 68 articles were included in our guidance development.

Based on this evidence and expert consensus, we developed 20 recommendations addressing indications for genetic testing in hereditary ataxia, components of pre- and post-test counseling, testing options, insurance considerations, interpretation of test results, and appropriate referral to genetic counseling services. Major themes include the importance of formal genetic counseling and suggesting whole genome sequencing as first-line testing, with an emphasis on detecting repeat expansions.

These evidence-based, consensus-driven recommendations aim to support clinicians in evaluating patients with unexplained ataxia in order to provide timely evaluation and care, both for patients and their at-risk relatives.