Genotype-Phenotype Relations for the Dystonia-Parkinsonism Genes , , , , and : MDSGene Systematic Review.

The Movement Disorders Society recommends the DYT/PARK prefix for genes where dystonia and parkinsonism are prominent in approximately half or more of patients. This systematic review explores the genotype-phenotype correlations of , , , , and -recently classified as DYT and historically linked to dystonia-parkinsonism. We searched PubMed and the Human Gene Mutation Database using standardized terms, including English-language, peer-reviewed publications up to February 2024. Following the MDSGene protocol, we extracted individual-level data on patients with biallelic pathogenic variants and at least one movement disorder. Features were marked "missing" if not explicitly reported. Of 1828 articles, 128 were eligible. We identified 386 patients and 262 variants. The median age at onset was 3 years for , 3 months for , 2.5 years for , 1.5 years for , and 16 years for . Missing data may reflect underreporting of negative findings. Case reports/serie, may bias toward atypical presentations. Our analysis showed dystonia-parkinsonism predominates in and , while , , and show predominantly dystonic phenotypes with a low frequency of parkinsonism. Ataxia was common in and . Awareness of these phenotypes is essential for early diagnosis and intervention, particularly in treatable conditions like or . The predominantly dystonic phenotype in , , and suggest that the DYT prefix may be more appropriate, highlighting the need to reconsider their nomenclature, and the importance of systematic reviews.