CASE REPORT
Heterozygous de novo mutation in the ATP1A2 gene in a patient with alternating hemiplegia of childhood
1
Independent Laboratory of Genetic Diagnostic, Medical University of Lublin, Lublin, Poland
2
Internal Disease Department, Warsaw Southern Hospital, Warsaw, Poland
3
MedGen Medical Centre, Warsaw, Poland.
4
Department of Pediatric Neurology, Medical University of Lublin, Lublin, Poland
Submission date: 2023-01-23
Final revision date: 2023-04-10
Acceptance date: 2023-04-12
Publication date: 2023-09-29
Pediatr Pol 2023;98(3):258-263
KEYWORDS
TOPICS
ABSTRACT
Alternating hemiplegia of childhood (AHC) is characterized by recurrent hemiplegic episodes and paroxysmal disorders, dystonia, nystagmus, epileptic seizure, mental retardation, and intellectual impairment. Alternating hemiplegia of childhood is caused by pathogenic variants in the genes encoding α-1, -2, and -3 subunits of Na,K-ATPase. Among them, pathogenic variants in ATP1A3 are responsible for almost 80% of cases. The aim of our study was to present a patient with de novo ATP1A2 mutation as the primary cause of AHC and to study the spectrum of phenotypes associated with mutation in this gene. Our study presents a case of a 9-year-old boy who was correctly diagnosed with AHC at the age of 8 years. The example of our patient proves that pathogenic variants in ATP1A2 correlate with milder phenotype.
REFERENCES (14)
1.
Rosewich H, Thiele H, Ohlenbusch A, et al. Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. Lancet Neurol 2012; 11: 764-773. .
2.
Verret S, Steele JC. Alternating hemiplegia in childhood: a report of eight patients with complicated migraine beginning in infancy. Pediatrics 1971; 47: 675–680. .
3.
Krägeloh I, Aicardi J. Alternating hemiplegia in infants: report of five cases. Dev Med Child Neurol 1980; 22: 784-791.
4.
Mikati MA, Panagiotakaki E, Arzimanoglou A. Revision of the diagnostic criteria of alternating hemiplegia of childhood. Eur J Paediatr Neurol 2021; 32: A4-A5.
5.
Swoboda KJ, Kanavakis E, Xaidara A, et al. Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation. Ann Neurol 2004; 55: 884-887.
6.
Wilbur C, Buerki SE, Guella I, et al. An Infant with epilepsy and recurrent hemiplegia due to compound heterozygous variants in ATP1A2. Pediatr Neurol 2017; 75: 87-90.
7.
Huang D, Liu M, Wang H, et al. De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene–disease relationship and variant classification: a case report. BMC Med Genomics 2021; 14: 95.
8.
Calame DG, Houck K, Lotze T, Emrick L, Parnes M. A novel ATP1A2 variant associated with severe stepwise regression, hemiplegia, epilepsy and movement disorders in two unrelated patients. Eur J Paediatr Neurol 2021; 31: 21-26.
9.
Roid GH, Sajewicz-Radtke U, Radtke BM, Lipowska M. Skale inteligencji Stanford-Binet (ed. 5). Pracownia Testów Psychologicznych i Pedagogicznych, Gdańsk 2017.
10.
Sweadner KJ, Arystarkhova E, Penniston J, Swoboda K. Genotype-structure-phenotype relationships diverge in paralogs ATP1A1, ATP1A2, and ATP1A3. Neurol Genet 2019; 5: e303.
11.
Li Y, Tang W, Kang L, et al. Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms. J Headache Pain. 2021; 22: 92.
12.
Todt U, Dichgans M, Jurkat-Rott K, et al. Rare missense variants in ATP1A2 in families with clustering of common forms of migraine. Hum Mutat 2005; 26: 315-321.
13.
Masoud M, Prange L, Wuchich J, Hunanyan A, Mikati MA. Diagnosis and treatment of alternating hemiplegia of childhood. Curr Treat Options Neurol 2017; 19: 8.
14.
Vetro A, Nielsen HN, Holm R, et al. ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria. Brain 2021; 144: 1435-1450.
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
