Objective: We reviewed the Movement Disorder Society Genetic mutation database (MDSGene) to evaluate the prevalence, clinical features and evolution of genetic conditions presenting with isolated or combined tremor.

Background: Several genetic conditions may present with tremor, either in isolation or as prominent clinical manifestation. There is limited data on the prevalence and clinical characteristics of monogenic movement disorders manifesting with tremor at onset.

Method: We gathered data from MDSGene (last search in July 2025). This database includes 58 genes associated with movement disorders syndromes from 2258 publications. ATP1A3, GBA1, PINK1, and ANO3 genes from MDSGene were not updated or did not include clinical data at the time of the search, hence PubMed literature review using ‘gene identifiers’ search terms was performed, screened for tremor prevalence at onset (isolated or combined) and over the disease course. Cases with isolated tremor at onset were further analysed for demographic, clinical and genetic characteristics.

Results: Screening of 25248 subjects revealed that the prevalence of tremor at any time as part of a genetically determined movement disorder syndrome was 9% (N=2314), of which 854 (3%) presented with tremor at onset. Isolated tremor at onset occurred in 2% of subjects (470/25248): Mean age at onset was 44±18 years. 66% had a family history of tremor or other movement disorders. Variants in nineteen genes were associated with isolated tremor at onset: the most frequent ones were LRRK2 (49%), PRKN (30%), GBA1 (5%), PINK1 (5%), GCH1 (4%), ANO3 (2%), TAF1 (2%), and TOR1A (1%). The most common motor disorder developed after isolated tremor was parkinsonism (93%), postural instability (30%); Non-motor symptoms involved neuropsychiatric (19.5%), cognitive (11%), sleep (12%). Most genetically determined isolated tremor syndromes at onset featured either single nucleotide (66%) or copy number variants (32%); 54% had dominant and 34% had recessive inheritance; 88% were definitely and 12% were possibly/probably pathogenic.

Conclusion: Tremor is uncommon in genetically determined movement disorders syndromes, especially isolated tremor at onset. Adult subjects presenting with tremor in early adulthood should be carefully phenotyped and genetic screening for parkinsonism and dystonia syndromes should be considered.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-disorders-presenting-with-tremor-at-onset-mdsgene-systematic-literature-review/