Variants of ATP1A3 in residue 756 cause a separate phenotype of relapsing encephalopathy with cerebellar ataxia (RECA)-Report of two cases and literature review.
ATP1A3
cerebellar ataxia
hypotonia
relapsing encephalopathy
whole-exome sequencing
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
13
05
2021
accepted:
08
07
2021
pubmed:
4
8
2021
medline:
17
3
2022
entrez:
3
8
2021
Statut:
ppublish
Résumé
Variants in ATP1A3 cause well-known phenotypes-alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss (CAPOS), and severe early infantile epileptic encephalopathy. Recently, there has been growing evidence for genotype-phenotype correlations in the ATP1A3 variants, and a separate phenotype associated with variants in residue 756-two acronyms are proposed for the moment-FIPWE (fever-induced paroxysmal weakness and encephalopathy) and RECA (relapsing encephalopathy with cerebellar ataxia). Herein, we are describing two new pediatric cases with a p.Arg756His change in the ATP1A3 gene. Both patients have had more than one episode of a neurological decompensation triggered by fever with severe hypotonia and followed by ataxia. Thirty-three cases from literature were analyzed to define and strengthen the genotype-phenotype correlation of variants located in residue 756 (p.Arg756His, p.Arg756Cys, p.Arg756Leu). Patients with a ATP1A3 variant in residue 756 are characterized by recurrent paroxysmal episodes of neurological decompensations triggered by fever, with severe hypotonia, ataxia, dysarthria, symptoms from the orofacial area (dysphagia, drooling) as well as with altered consciousness. Recovery is slow and usually not full with the persistent symptoms of cerebellar ataxia, dysarthria, dystonic and choreiform movements.
Sections du résumé
BACKGROUND
Variants in ATP1A3 cause well-known phenotypes-alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss (CAPOS), and severe early infantile epileptic encephalopathy. Recently, there has been growing evidence for genotype-phenotype correlations in the ATP1A3 variants, and a separate phenotype associated with variants in residue 756-two acronyms are proposed for the moment-FIPWE (fever-induced paroxysmal weakness and encephalopathy) and RECA (relapsing encephalopathy with cerebellar ataxia).
MATERIALS AND METHODS
Herein, we are describing two new pediatric cases with a p.Arg756His change in the ATP1A3 gene. Both patients have had more than one episode of a neurological decompensation triggered by fever with severe hypotonia and followed by ataxia. Thirty-three cases from literature were analyzed to define and strengthen the genotype-phenotype correlation of variants located in residue 756 (p.Arg756His, p.Arg756Cys, p.Arg756Leu).
CONCLUSIONS
Patients with a ATP1A3 variant in residue 756 are characterized by recurrent paroxysmal episodes of neurological decompensations triggered by fever, with severe hypotonia, ataxia, dysarthria, symptoms from the orofacial area (dysphagia, drooling) as well as with altered consciousness. Recovery is slow and usually not full with the persistent symptoms of cerebellar ataxia, dysarthria, dystonic and choreiform movements.
Identifiants
pubmed: 34342181
doi: 10.1002/mgg3.1772
pmc: PMC8457706
doi:
Substances chimiques
ATP1A3 protein, human
0
Sodium-Potassium-Exchanging ATPase
EC 7.2.2.13
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1772Informations de copyright
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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