Genotype-dependent response to combined levodopa/benserazide and trihexyphenidyl in pediatric genetic dystonia.

BACKGROUND

Genetic etiologies underlie a substantial proportion of pediatric dystonia, but whether treatment response to combined dopaminergic and anticholinergic therapy varies by genotype remains unknown.

METHODS

This retrospective cohort study analyzed 36 children with genetically confirmed dystonia, classified into three subgroups: PANK2 (n = 7), channelopathies (SCN1A/SCN2A/SCN3A/SCN1B, KCNQ2; n = 6), and other monogenic etiologies (n = 23; 19 distinct genes). All received levodopa/benserazide and trihexyphenidyl combination therapy for 16 weeks. Outcomes included Barry-Albright Dystonia Scale (BADS), Gross Motor Function Measure-88 (GMFM-88), Quality of Upper Extremity Skills Test (QUEST), and Cerebral Palsy Quality of Life Questionnaire (CP-QOL).

RESULTS

Treatment response was genotype-dependent. PANK2 patients showed excellent improvement (ΔBADS -6.6 ± 3.0; ΔGMFM-88 + 49.6 ± 45.8). Other monogenic patients showed moderate improvement comparable to our cerebral palsy cohort (ΔBADS -6.1 ± 1.9; ΔGMFM-88 + 32.2 ± 26.5). Channelopathy patients derived minimal benefit (ΔBADS -3.5 ± 1.2; ΔGMFM-88 + 6.2 ± 2.9; p < 0.001 compared to both other groups). All six patients with status dystonicus (all in the other monogenic group) responded excellently. Adverse event rates were comparable across groups (p = 0.61).

CONCLUSIONS

Genotype determines treatment response to levodopa/benserazide and trihexyphenidyl in pediatric genetic dystonia. PANK2 and most other monogenic etiologies respond well, while channelopathies derive minimal benefit. Genotype, not severity, guides therapy.