This largest GNAO1-RD cohort and first longitudinal natural history study provide insights into disease progression. GNAO1-RD generally follows a non-degenerative course, showing stability or mild improvements over time in cognition, language, adaptive skills, and motor function. Importantly, although global severity scores remained stable overall, severe cases showed cumulative functional burden driven by progressive movement disorder, rather than global neurodegeneration. Mortality occurred in a subset of patients because of complications from dyskinetic crises, infections, and epilepsy-related events. Genotype-phenotype data and the GNAO1-RD severity score support early risk stratification and personalized treatment development. ANN NEUROL 2026.
Domínguez‐Carral et al. (Fri,) studied this question.