Mutational and phenotypic expansion of ATP1A3-related disorders: Report of nine cases.
ATP1A3
Alternating hemiplegia of childhood
Epilepsy
Epileptic encephalopathy
Hemiplegia-hemiconvulsion-epilepsy syndrome
Neurogeneration with brain iron accumulation
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
30 Jul 2020
30 Jul 2020
Historique:
received:
17
09
2019
revised:
18
04
2020
accepted:
23
04
2020
pubmed:
28
4
2020
medline:
25
6
2020
entrez:
28
4
2020
Statut:
ppublish
Résumé
Mutations in the ATP1A3 gene are known to be the cause of three distinct neurological syndromes including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP) and cerebellar ataxia, arefexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS). Recent studies have suggested the broader diversity of ATP1A3-related disorders. This study aimed to investigate the clinical spectrum in patients carrying causative mutations within the ATP1A3 gene. The medical histories of nine unrelated patients with diverse phenotypes harboring variants in ATP1A3 were retrospectively analyzed after they were referred to a tertiary epilepsy center in one of the two different health care systems (Germany or Thailand). Clinical features, neurophysiological data, imaging results, genetic characteristics and treatments were reviewed. Three patients harbor novel mutations in the ATP1A3 gene. Atypical clinical features and imaging findings were observed in two cases, one with hemiplegia-hemiconvulsion-epilepsy syndrome, and the other with neurodegeneration with brain iron accumulation. All nine patients presented with intellectual impairment. Alternating hemiplegia of childhood (AHC) was the most common phenotype (67%). Flunarizine and topiramate led to symptom reduction in 83% and 25% of AHC cases administered, respectively. The present case series expands the clinical and genetic spectrum of ATP1A3-related disorders.
Sections du résumé
BACKGROUND
BACKGROUND
Mutations in the ATP1A3 gene are known to be the cause of three distinct neurological syndromes including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP) and cerebellar ataxia, arefexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS). Recent studies have suggested the broader diversity of ATP1A3-related disorders. This study aimed to investigate the clinical spectrum in patients carrying causative mutations within the ATP1A3 gene.
METHOD
METHODS
The medical histories of nine unrelated patients with diverse phenotypes harboring variants in ATP1A3 were retrospectively analyzed after they were referred to a tertiary epilepsy center in one of the two different health care systems (Germany or Thailand). Clinical features, neurophysiological data, imaging results, genetic characteristics and treatments were reviewed.
RESULTS
RESULTS
Three patients harbor novel mutations in the ATP1A3 gene. Atypical clinical features and imaging findings were observed in two cases, one with hemiplegia-hemiconvulsion-epilepsy syndrome, and the other with neurodegeneration with brain iron accumulation. All nine patients presented with intellectual impairment. Alternating hemiplegia of childhood (AHC) was the most common phenotype (67%). Flunarizine and topiramate led to symptom reduction in 83% and 25% of AHC cases administered, respectively.
CONCLUSION
CONCLUSIONS
The present case series expands the clinical and genetic spectrum of ATP1A3-related disorders.
Identifiants
pubmed: 32339621
pii: S0378-1119(20)30378-4
doi: 10.1016/j.gene.2020.144709
pii:
doi:
Substances chimiques
ATP1A3 protein, human
0
Sodium-Potassium-Exchanging ATPase
EC 7.2.2.13
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
144709Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.