1. Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review
- Author
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Vincenzo Leuzzi, Maria Luigia Gambardella, Laura Cantonetti, Enrico Bertini, Claudia Barassi, Lorena Travaglini, Carlo Efisio Marras, Loreto Rios, Federica Graziola, Domenica Battaglia, Giacomo Garone, Claudia Castiglioni, Tommaso Schirinzi, Enrico Castelli, Alessandro Capuano, Serena Galosi, and Gessica Vasco
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Movement disorders ,Movement disorder emergencies ,GTP-Binding Protein alpha Subunits, Gi-Go ,Hyperkinesis ,GNAO1 ,Gi-Go ,03 medical and health sciences ,0302 clinical medicine ,Settore MED/39 - NEUROPSICHIATRIA INFANTILE ,Children movement disorders ,Chorea ,Medicine ,Humans ,Age of Onset ,Status dystonicus ,Child ,Preschool ,Loss function ,Genetic Association Studies ,Dystonia ,Dyskinesias ,Epilepsy ,Movement Disorders ,business.industry ,Statusdy stonicus ,Brain ,Infant ,medicine.disease ,GTP-Binding Protein alpha Subunits ,030104 developmental biology ,Neurology ,Dyskinesia ,Child, Preschool ,Cohort ,Disease Progression ,Neurology (clinical) ,Geriatrics and Gerontology ,medicine.symptom ,Emergencies ,business ,030217 neurology & neurosurgery - Abstract
GNAO1 variants were recently discovered as causes of epileptic encephalopathies and heterogeneous syndromes presenting with movement disorders (MDs), whose phenomenology and clinical course are yet undefined. We herein focused on GNAO1-related MD, providing an analytical review of existing data to outline the main MD phenomenology and management, clinical evolution and genotype-phenotype correlations. Reviewing 41 previously published patients and assessing 5 novel cases, a comprehensive cohort of 46 patients was analyzed, reassuming knowledge about genotypes, phenotypes, disease course and treatment of this condition. GNAO1-related MD consisted of a severe early-onset hyperkinetic syndrome, with prominent chorea, dystonia and orofacial dyskinesia. Symptoms are poorly responsive to medical therapy and fluctuate, with critical and life-threatening exacerbations, such as status dystonicus. The presence of a choreiform MD appears to be predictive of a higher risk of movement disorder emergency. Surgical treatments are sometimes effective, although severe disabilities persist. Differently from the early infantile epileptic encephalopathy phenotype (associated with loss of function variants), no clear correlation between genotype and MD phenotype emerged, although some variants recurred more frequently, mainly affecting exons 6 and 7.
- Published
- 2019