Clinical and genetic profile of lower limb dystonia: a dual-center retrospective study in China

Background Lower limb dystonia (LLD) is a clinically significant form of dystonia that can substantially impair gait and quality of life. Its clinical presentation is highly heterogeneous, and investigations into underlying genetic causes remain limited. This study aimed to characterize the clinical and genetic profile of LLD in a Chinese cohort and to explore potential genotype–phenotype correlations. Methods Patients diagnosed with LLD without an acquired cause were retrospectively enrolled at two movement disorder centers in China between January 2016 and December 2024. Clinical characteristics were collected, and genetic testing results were comprehensively analyzed. Results A total of 68 patients with LLD without an acquired cause were included. The median age at dystonia onset was 14.0 years (IQR, 6.3–23.0 years), with 46 patients (67.6%) developing symptoms before the age of 20 years. Foot dystonia was the most common initial manifestation, presenting as foot inversion (25.0%) and foot plantarflexion (20.6%). At the last follow-up, 35 patients (51.5%) remained restricted to lower limbs involvement (LLD group), whereas the remaining 33 patients (48.5%) developed dystonia spreading to other anatomical regions (LLD-plus group). Pathogenic or likely pathogenic variants were identified in 29 patients (42.6%), involving TOR1A ( n = 8), GCH1 ( n = 6), KMT2B ( n = 5), PRKN ( n = 5), TH ( n = 2), SGCE ( n = 1), PINK1 ( n = 1), and PANK2 ( n = 1). The distribution of causative genes differed between the two groups. GCH1 and PRKN were the most frequently implicated genes in the LLD group, whereas TOR1A and KMT2B were the predominant causative genes in the LLD-plus group. Conclusion LLD in the Chinese cohort is a clinically and genetically heterogeneous disorder, with a substantial proportion of patients harboring identifiable monogenic causes.