Objective: Within the Movement Disorder Society the Task Force on Genetic Nomenclature has developed several gene panels for different movement disorders to give guidance to clinicians, however not yet for the most common movement disorder: tremor. The aim of this systematic review is to present all causal genes related to tremor syndromes, assign them to their main accompanying feature and in this way create a gene list which could be used as a gene panel in clinical practice.

Background: To classify tremor according to the Tremor Study Group’s consensus statement of the International Parkinson and Movement Disorder Society, genetics play an important role in determining its etiology (axis II). In the last decade technological developments in the field of genetics rapidly evolved, producing an excessive growth in the number of reported causative genes in genetically heterogeneous diseases, including movement disorders. Since the number of publications on causative genes related to tremor is still growing expansively, it is increasingly difficult even for movement disorder specialists to follow and interpret these results.

Method: We conducted a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method up to the 1^st of January 2021. We included studies showing a causative relationship between the gene abnormality and the development of tremor. Tremor did not necessarily have to be the main movement disorder. A gene is reported when multiple unrelated individuals are shown to have the mutation or when there are at least two families with this causal mutation.

Results: A total of 254 studies were included, reporting a total of 75 causative genes for tremor. To obtain a better overview, we assigned these genes to their main accompanying feature: parkinsonism (e.g. PARK-LRRK2, PARK-parkin), ataxia (e.g. SCA-ATXN1, FMR1), dystonia (e.g. DYT-TOR1A, DYT-ATP7B), myoclonus (e.g. SAMD12, STARD7), neurodevelopmental delay (e.g. CUL4B, NUBPL), neuropathy (e.g. AR, GBA), metabolic-related disorders (e.g. TSHR, NBIA/DYT/PARK-CP).

Conclusion: Isolated tremor syndromes have no genetic cause, as far as known to date. However, tremor can be the presenting symptom of combined tremor disorders. This review lists genetically induced combined tremor disorders, and by categorising them based on their main accompanying feature supports clinicians in diagnosing tremor etiologically.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tremor-genetics-in-clinical-practice-a-systematic-literature-review/