Dados do Trabalho

Título

DISORDERS RELATED TO ATP1A3: A GENE WITH MULTIPLE FACETS

Apresentação do caso único

A 5-year-old male patient, the first child of non-consanguineous parents, with no prenatal or perinatal complications and no relevant family history. He developed epilepsy in the neonatal period and, at 11 months, starts with recurrent self-limited episodes of alternating hemiparesis, lasting from minutes to days. He showed global developmental delay, starting to walk at three years, and spoke his first words at two years, with poor social interaction. A molecular test detected the presence of a pathogenic heterozygous variant in the ATP1A3 gene: c.2440G>A;p.Asp801Asn. With the introduction of Flunarizine, the patient showed improvement in the frequency of hemiparesis episodes. Additionally, he uses Carbamazepine and Clobazam, with reduction in epileptic events.

Discussão

Alternating Hemiplegia of Childhood most frequently manifests in the first decade of life and is characterized by repeated, transient episodes of paresis or plegia on one or both sides of the body, which may be accompanied by developmental delay, epilepsy, and movement disorders. It is one of the phenotypes classically associated with the ATP1A3 gene. Besides it, rapid-onset dystonia parkinsonism and cerebellar ataxia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome) were the first described phenotypes. However, an increasing number of specific phenotypes are being observed, such as Relapsing Encephalopathy With Cerebellar Ataxia, Fever-Induced Paroxysmal Weakness and Encephalopathy; Early Life Epilepsy with or without polymicrogyria; Dystonia, Dysmorphism, Encephalopathy, MRI Abnormalities, and no Hemiplegia; and Childhood-Onset Schizophrenia. Other clinical conditions have also been reported, such as spastic paraparesis and congenital hydrocephalus. Although the classic syndromes have specific clinical criteria, an expanding number of cases demonstrate atypical and overlapping features and the mechanisms of pathogenicity are not yet totally elucidated.

Comentários finais

Neurological disorders associated with the ATP1A3 gene present multiple facets. It has been proposed that they represent a continuum of different manifestations across a broad clinical spectrum. It is crucial to consider this diagnosis in patients with movement disorders, weakness, epilepsy, and encephalopathy, especially with rapid onset or triggers. It is also necessary to seek to understand this gene to assist patients effectively.

Referências

Salles PA, Mata IF, Brünger T, Lal D, Fernandez HH. ATP1A3-Related Disorders: An Ever-Expanding Clinical Spectrum. Front Neurol. 2021 Apr 1;12:637890. doi: 10.3389/fneur.2021.637890. PMID: 33868146; PMCID: PMC8047318.
Sweney MT, Newcomb TM, Swoboda KJ. The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond. Pediatr Neurol. 2015 Jan;52(1):56-64. doi: 10.1016/j.pediatrneurol.2014.09.015. Epub 2014 Oct 13. PMID: 25447930; PMCID: PMC4352574.
Vezyroglou A, Akilapa R, Barwick K, Koene S, Brownstein CA, Holder-Espinasse M, Fry AE, Németh AH, Tofaris GK, Hay E, Hughes I, Mansour S, Mordekar SR, Splitt M, Turnpenny PD, Demetriou D, Koopmann TT, Ruivenkamp CAL, Agrawal PB, Carr L, Clowes V, Ghali N, Holder SE, Radley J, Male A, Sisodiya SM, Kurian MA, Cross JH, Balasubramanian M. The Phenotypic Continuum of ATP1A3-Related Disorders. Neurology. 2022 Oct 4;99(14):e1511-e1526. doi: 10.1212/WNL.0000000000200927. Epub 2022 Jul 18. PMID: 36192182; PMCID: PMC9576304.

Palavras Chave

ATP1A3 gene mutation; ATP1A3 neurological disorders; Alternating hemiplegia of childhood