UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome

Danti, FR; Galosi, S; Romani, M; Montomoli, M; Carss, KJ; Raymond, FL; Parrini, E; ... Guerrini, R; + view all (2017) GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome. Neurology Genetics , 3 (2) , Article e143. 10.1212/NXG.0000000000000143. Green open access

[img]
Preview
Text
Kurian_Neurol Genet-2017-Danti-.pdf - ["content_typename_Published version" not defined]

Download (868kB) | Preview

Abstract

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia.

Type: Article
Title: GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/NXG.0000000000000143
Publisher version: http://doi.org/10.1212/NXG.0000000000000143
Language: English
Additional information: Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health > Maternal and Fetal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/1550505
Downloads since deposit
57Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item