|
Title
|
|
|
|
RHOBTB2 mutations expand the phenotypic spectrum of alternating hemiplegia of childhood
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Objective: To explore the phenotypic spectrum of RHOBTB2-related disorders, and specifically to determine whether patients fulfil criteria for alternating hemiplegia of childhood (AHC), we report the clinical features of 11 affected individuals. Methods: Individuals with RHOBTB2-related disorders were identified through a movement disorder clinic at a specialist paediatric centre, with additional cases identified through collaboration with other centres internationally. Clinical data was acquired through retrospective case-note review. Results: 11 affected patients were identified. All had heterozygous missense variants involving exon 9 of RHOBTB2, confirmed as de novo in nine cases. All had a complex motor phenotype, including at least two different kinds of movement disorder, e.g. ataxia and dystonia. Many patients demonstrated several features fulfilling the criteria for AHC: 10 patients had a movement disorder including paroxysmal elements and eight experienced hemiplegic episodes. In contrast to classical AHC, commonly caused by mutations in ATP1A3, these events were only reported later in RHOBTB2-mutation-positive patients, from twenty months of age. Seven patients had epilepsy, but of these, four achieved seizure-freedom. All patients had intellectual disability, usually moderate to severe. Other features include episodes of marked skin colour change and gastrointestinal symptoms, each in four patients. Conclusion: Although heterozygous RHOBTB2 mutations were originally described in early infantile epileptic encephalopathy (EIEE64), our study confirms that they account for a more expansive clinical phenotype, including a complex polymorphic movement disorder with paroxysmal elements resembling AHC. RHOBTB2 testing should therefore be considered in patients with an AHC-like phenotype, particularly those negative for ATPA1A3 mutations. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Neurology / American Academy of Neurology. - Minneapolis, Minn
| |
|
Publication
|
|
|
|
Minneapolis, Minn
:
2021
| |
|
ISSN
|
|
|
|
0028-3878
| |
|
DOI
|
|
|
|
10.1212/WNL.0000000000011543
| |
|
Volume/pages
|
|
|
|
96
:11
(2021)
, p. e1539-e1550
| |
|
ISI
|
|
|
|
000657054600018
| |
|
Pubmed ID
|
|
|
|
33504645
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|