Genetics of cerebellar disorders

Abstract The approach to identifying a genetic cause in patients with cerebellar disorders relies on history, examination, consultation, and testing, combined with specialized expertise because they are rare and genetically diverse. Cerebellar disorders can be caused by a variety of DNA alterations including single-nucleotide changes, small insertions or deletions, larger copy number variants, and nucleotide repeat expansions, exhibiting autosomal-recessive, autosomal-dominant (inherited and de novo ), X-linked, and mitochondrial modes of inheritance. Imaging findings and a variety of neurologic and nonneurologic clinical features can help direct genetic testing and choose the most appropriate strategy. Clinical and genetic diagnoses are complementary, each providing distinct information for the care of the patient. In this chapter, we provide an overview of inheritance modes for different cerebellar disorders and the variety of genetic testing and tools that are currently available to reach a genetic diagnosis, including conventional and next-generation sequencing, classic, molecular and virtual cytogenetics, testing for repeat expansions, and other techniques. Practical examples are presented in both the text and accompanying vignettes.