Abstract:

Objective To investigate the genotypes and phenotypes features of patients with GNAO1 gene variants. Methods Genetic features, clinical manifestations and therapeutic reaction of five patients with GNAO1 gene variants were retrospectively analyzed. Results A total of 5 patients with GNAO1 gene variants were detected, including 4 patients with missense variants and 1 with splice site variation. Three variants were reported previously and two were novel variants. Two children presented with early-onset infantile epileptic encephalopathy with varying degrees of dyskinesia; three children presented with extrapyramidal symptoms (two with dystonia and one with choreoathetosis) and no seizures for the time being; profound developmental delay was observed in all five patients. Two patients with epilepsy did not response to multiple antiepileptic drugs. Two patients with dystonia underwent deep brain stimulation (DBS) therapy. The BFMDRS score decreased by 32.36% one month after surgery in one patient. However, no significant improvement was found in the other patient, and the BFMDRS score decreased by only 7.79% at 12 months postoperatively. One patient with choreoathetosis intended to accept DBS treatment later. Conclusions The majority of GNAO1 gene variants were missense mutation. The clinical manifestations of patients with GNAO1 gene variants were various, mainly presenting with developmental delay, movement disorders, and/or epilepsy. The epilepsy and the extrapyramidal symptoms responded poorly to the medical therapy, and DBS treatment could alleviate the dyskinesia in some patients.

Key words: GNAO1 gene, developmental delay, extrapyramidal symptoms, epilepsy, deep brain stimulation