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Classical phenotypes include alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), and syndrome characterized by cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS). Additional rarer forms include childhood-onset-schizophrenia (COS), encephalopathy with MRI abnormalities without hemiplegia (D-DEM\u00d8), fever-induced paroxysmal weakness and encephalopathy (FIPWE), and relapsing encephalopathy with cerebellar ataxia (RECA). These conditions often overlap, sharing core symptoms due to dysfunction of the Na\u207a\/K\u207a-ATPase \u03b13 subunit. Some mutations result in a thermolabile enzyme, which impairs its function under stress, leading to weakness\u2019 episodes, encephalopathy and ataxia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case series<\/jats:title>\n                    <jats:p>We report a patients\u2019 cohort with ATP1A3 mutations followed at Santobono-Pausilipon Children\u2019s Hospital in Naples. The first family includes three siblings with RECA (p.Arg756Cys). The second cluster comprises a mother and son with FIPWE (p.Arg756His). We also describe one case of AHC (p.Asp801Asn) and one of CAPOS (p.Arg756Cys). All patients showed marked susceptibility to infection and fever.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>Our case series confirms the complex clinical scenarios in ATP1A3-related disorders, with symptoms overlapping and possible interfamilial variability, contributing to the diagnostic challenge posed by a rare genetic disorder, already observed in individuals with ATP1A3 gene mutations. The ongoing effort to characterize the clinical phenotype and identify \u201ccore\u201d symptoms is necessary to expand our knowledge of the genotype-phenotype correlation, which is currently unclear. More importantly, our series highlights the molecular fragility of mutant ATP1A3, particularly its sensitivity to fever. Proactive prevention of fever and time management may be crucial to reducing the risk of neurological deterioration in affected individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-026-09101-5","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:42:48Z","timestamp":1779151368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ATP1A3-related syndromes: our case-series unveiling a dynamic, fever-triggered and overlapping array of neurological phenotypes"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8980-1120","authenticated-orcid":false,"given":"G.","family":"Errichiello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bernardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Acquaviva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Troisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Bargiacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rubino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Carotenuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Varone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"D\u2019Acunto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"issue":"14","key":"9101_CR1","doi-asserted-by":"publisher","first-page":"e1511","DOI":"10.1212\/WNL.0000000000200927","volume":"99","author":"A Vezyroglou","year":"2022","unstructured":"Vezyroglou A, Akilapa R, Barwick K, Koene S, Brownstein CA, Holder-Espinasse M, Balasubramanian M (2022) The phenotypic continuum of ATP1A3-related disorders. 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