Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review

Tommaso Schirinzi, Giacomo Garone, Lorena Travaglini, Gessica Vasco, Serena Galosi, Loreto Rios, Claudia Castiglioni, Claudia Barassi, Domenica Battaglia, Maria Luigia Gambardella, Laura Cantonetti, Federica Graziola, Carlo Efisio Marras, Enrico Castelli, Enrico Bertini, Alessandro Capuano, Vincenzo Leuzzi

Research output: Contribution to journalReview article

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 languageEnglish
JournalParkinsonism and Related Disorders
DOIs
Publication statusE-pub ahead of print - Nov 16 2018

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Movement Disorders
Chorea
Brain Diseases
Phenotype
Genotype
Dystonia
Dyskinesias
Genetic Association Studies
Attention Deficit Disorder with Hyperactivity
Exons
Emergencies
Therapeutics

Cite this

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 journalReview article

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. / Phenomenology and clinical course of movement disorder in GNAO1 variants : Results from an analytical review. In: Parkinsonism and Related Disorders. 2018.
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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.",
author = "Tommaso Schirinzi and Giacomo Garone and Lorena Travaglini and Gessica Vasco and Serena Galosi and Loreto Rios and Claudia Castiglioni and Claudia Barassi and Domenica Battaglia and Gambardella, {Maria Luigia} and Laura Cantonetti and Federica Graziola and Marras, {Carlo Efisio} and Enrico Castelli and Enrico Bertini and Alessandro Capuano and Vincenzo Leuzzi",
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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.

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DO - 10.1016/j.parkreldis.2018.11.019

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JO - Parkinsonism and Related Disorders

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