GNAO1 Haploinsufficiency: The Milder End of the GNAO1 Phenotypic Spectrum

GNAO1 variants are typically associated with severe, early-onset movement disorders (MDs) with life-threatening and drug-resistant paroxysmal exacerbations, neurodevelopmental disorders, and epilepsy. Recently, the phenotypic spectrum has broadened to include milder phenotypes with late-onset dystonia, minor cognitive impairment, and other neurological signs, including parkinsonism and myoclonus. GNAO1 haploinsufficiency has been evoked as a putative mechanism underlying milder clinical presentations.1, 2 To date, however, the functional consequences of this class of variants have not yet been evaluated.