Work

CAPOS and Beyond: ATP1A3 Variants in Pediatric Movement Disorders – Case Reports

Year: 2025

Type: article

Abstract: Introduction: ATP1A3-related disorders encompass a clinically heterogeneous spectrum that includes previously defined dominantly inherited phenotypes such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome, as well as more complex and overlapping presentations. Case Presentation: In this study, we present 2 pediatric cases that expand the phenotypic and genotypic spectrum of ATP1A3-associated disease. Both patients presented with “Guillain-Barré syndrome (GBS)-like episodes” characterized by acute-onset encephalopathy, ataxia, areflexia, and sensorimotor deterioration following febrile infections. Prominent paroxysmal postural abnormalities and dystonia were noted in both cases; however, the overall clinical features blurred the classical boundaries between CAPOS and other ATP1A3-associated phenotypes. The first patient carried the previously reported heterozygous ATP1A3(NM_001256214.2):c.2491G>A(p.Glu831Lys) variant, classically associated with CAPOS, and also exhibited sensorineural hearing loss with a positive family history. The second patient harbored a novel ATP1A3(NM_152296.5):c.2266C>T p.(Arg756Cys)(Clinvar: VCV000425189.38) variant and displayed oculomotor apraxia and chorea during episodes. Conclusion: These cases underscore the importance of considering ATP1A3 variants in children presenting with GBS-like features, infection-triggered neurological attacks, and mixed movement disorders. Our findings highlight the diagnostic value of genetic testing in atypical neuroregression syndromes and contribute to the recognition of “blended” ATP1A3 phenotypes beyond classical diagnostic entities. The novel pathogenic variant further supports ongoing efforts to refine genotype-phenotype correlations within this evolving group of neurological disorders.

Source: Molecular Syndromology

DOI: 10.1159/000549755

Authors: Mehpare Sarı Yanartaş, Özlem Yayıcı Köken, Ahmet Cevdet Ceylan, Ayşe Ergül Bozacı, Tuğçe Tural Kara, Şenay Haspolat

Institutions: Akdeniz University, Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital

Language: English

Topic: Hereditary Neurological Disorders

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W4416747106