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.
| Original language | English |
|---|---|
| Journal | Parkinsonism and Related Disorders |
| DOIs | |
| Publication status | E-pub ahead of print - Nov 16 2018 |
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Phenomenology and clinical course of movement disorder in GNAO1 variants : Results from an analytical review. / Schirinzi, Tommaso; Garone, Giacomo; Travaglini, Lorena; Vasco, Gessica; Galosi, Serena; Rios, Loreto; Castiglioni, Claudia; Barassi, Claudia; Battaglia, Domenica; Gambardella, Maria Luigia; Cantonetti, Laura; Graziola, Federica; Marras, Carlo Efisio; Castelli, Enrico; Bertini, Enrico; Capuano, Alessandro; Leuzzi, Vincenzo.
In: Parkinsonism and Related Disorders, 16.11.2018.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Phenomenology and clinical course of movement disorder in GNAO1 variants
T2 - Results from an analytical review
AU - Schirinzi, Tommaso
AU - Garone, Giacomo
AU - Travaglini, Lorena
AU - Vasco, Gessica
AU - Galosi, Serena
AU - Rios, Loreto
AU - Castiglioni, Claudia
AU - Barassi, Claudia
AU - Battaglia, Domenica
AU - Gambardella, Maria Luigia
AU - Cantonetti, Laura
AU - Graziola, Federica
AU - Marras, Carlo Efisio
AU - Castelli, Enrico
AU - Bertini, Enrico
AU - Capuano, Alessandro
AU - Leuzzi, Vincenzo
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2018/11/16
Y1 - 2018/11/16
N2 - 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.
AB - 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.
U2 - 10.1016/j.parkreldis.2018.11.019
DO - 10.1016/j.parkreldis.2018.11.019
M3 - Review article
C2 - 30642806
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -