Genetic movement disorders in patients of Jewish Ancestry

IMPORTANCE: Genetic diseases often cluster in different ethnic groups and may present with recognizable unique clinical manifestations. OBJECTIVE: To summarize current knowledge about movement disorders overrepresented among patients of Jewish ancestry. EVIDENCE REVIEW: We searched PubMed and the OMIM and Israeli National Genetic Databases for articles published from 1969 through March 31, 2014, using the search terms Parkinson's disease,movement disorders, ataxia, dystonia, chorea, and Creutzfeldt-Jakob with and Jewish. The final reference list was generated by giving priority to articles directly related to the topic, articles with the latest information, and comprehensive but relevant reviews. FINDINGS: About one-third of patients with sporadic Parkinson disease (PD) and more than 40% of patients with familial PD of Ashkenazi Jewish descent likely carry the G2019S mutation in the LRRK2 gene, a mutation in the glucocerebrosidase (GBA) gene, or both. This finding contrasts with only a 10%frequency of these mutations in patients with PD who are of non-Jewish ancestry. Adystonia due to a TOR1A gene mutation is responsible for most early-onset autosomal dominant dystonia, and 90% of Ashkenazi Jews who develop early-onset disease have TOR1A-related dystonia.Familial Creutzfeldt-Jakob disease and cerebrotendinous xanthomatosis tend to cluster among Jews of North African descent, and Machado-Joseph disease is particularly frequent in Yemenite Jews. CONCLUSIONSANDRELEVANCE: Genetic forms of PD are much more common in patients of Ashkenazi Jewish ancestry with sporadic and familial PD than in the non-Jewish population. The recognition of the particular movement disorder phenotype, coupled with information about the ethnic origin of the patients,may point to specific genetic testing and lead to early and correct diagnosis.