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The disorder is mainly caused by mutations in <jats:italic>ATP1A3<\/jats:italic> gene, and to a lesser extent in <jats:italic>ATP1A2<\/jats:italic> gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations\u00a0with intrafamilial variability.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>Clinical and genetic findings of a couple of twins (Family 1:\u00a0Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in <jats:italic>ATP1A3<\/jats:italic> gene (c.2318A&gt;G)\u00a0was detected. In siblings of Family 2, the younger brother showed a novel <jats:italic>GRIN2A<\/jats:italic> variant (c.3175\u2009T\u2009&gt;\u2009A), while the older carried the same <jats:italic>GRIN2A<\/jats:italic> variant, and two missense mutations in <jats:italic>SCNIB<\/jats:italic> (c.632\u2009&gt;\u2009A) and <jats:italic>KCNQ2<\/jats:italic> (1870\u2009G\u2009&gt;\u2009A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13052-021-01194-2","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T11:03:19Z","timestamp":1645095799000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability"],"prefix":"10.1186","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-9560","authenticated-orcid":false,"given":"Piero","family":"Pavone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xena Giada","family":"Pappalardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naira","family":"Mustafa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Yoon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Kyu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Incorpora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona Domenica","family":"Marino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Corsello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Parano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martino","family":"Ruggieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"issue":"4","key":"1194_CR1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1542\/peds.47.4.675","volume":"47","author":"S Verret","year":"1971","unstructured":"Verret S, Steele JC. 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