{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T12:09:51Z","timestamp":1769170191068,"version":"3.49.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient\u2019s needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics. Here we present a case series of 6 patients with classical A-T and variant A-T, which illustrates the phenotypic variability of A-T that can present in childhood with prominent extrapyramidal features, with or without cerebellar ataxia. We report the clinical data, together with a detailed genotype description, immunological analyses, and related expression of the ATM protein. We show that the presence of some residual ATM kinase activity leads to the clinical phenotype variant A-T that differs from the classical A-T. Our data illustrate that the diagnosis of the variant form of A-T can be delayed and difficult, while early recognition of the variant form as well as the classical A-T is a prerequisite for providing a correct prognosis and appropriate rehabilitation and support, including the avoidance of diagnostic X-ray procedures, given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment.<\/jats:p>","DOI":"10.3389\/fimmu.2022.791522","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T06:50:26Z","timestamp":1643352626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Childhood-Onset Movement Disorders Can Mask a Primary Immunodeficiency: 6 Cases of Classical Ataxia-Telangiectasia and Variant Forms"],"prefix":"10.3389","volume":"13","author":[{"given":"Geraldine","family":"Blanchard-Rohner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Peirolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludivine","family":"Coulon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Korff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre R.","family":"Burkhard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Gumy-Pause","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Ranza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Jandus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harpreet","family":"Dibra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander Malcolm R.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Fluss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41572-019-0113-0","article-title":"Chromosome Instability Syndromes","volume":"5","author":"Taylor","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)01796-8","article-title":"Ocular Manifestations of Ataxia-Telangiectasia","volume":"134","author":"Farr","year":"2002","journal-title":"Am J Ophthalmol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13020","article-title":"Ataxia-Telangiectasia: A Review of Clinical Features and Molecular Pathology","volume":"30","author":"Amirifar","year":"2019","journal-title":"Pediatr Allergy Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/B978-0-444-62702-5.00014-7","article-title":"Ataxia Telangiectasia","volume":"132","author":"Nissenkorn","year":"2015","journal-title":"Handb Clin Neurol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2013.04.012","article-title":"The Role of ATM and DNA Damage in Neurons: Upstream and Downstream Connections","volume":"12","author":"Herrup","year":"2013","journal-title":"DNA Repair (Amst)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181af33bd","article-title":"Clinical Spectrum of Ataxia-Telangiectasia in Adulthood","volume":"73","author":"Verhagen","year":"2009","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22016","article-title":"Presence of ATM Protein and Residual Kinase Activity Correlates With the Phenotype in Ataxia-Telangiectasia: A Genotype-Phenotype Study","volume":"33","author":"Verhagen","year":"2012","journal-title":"Hum Mutat"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25394","article-title":"Genotype, Extrapyramidal Features, and Severity of Variant Ataxia-Telangiectasia","volume":"85","author":"Schon","year":"2019","journal-title":"Ann Neurol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.jaci.2013.01.053","article-title":"Antibody Deficiency in Patients With Ataxia Telangiectasia Is Caused by Disturbed B- and T-Cell Homeostasis and Reduced Immune Repertoire Diversity","volume":"131","author":"Driessen","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03684.x","article-title":"Immunodeficiency in Ataxia Telangiectasia Is Correlated Strongly With the Presence of Two Null Mutations in the Ataxia Telangiectasia Mutated Gene","volume":"153","author":"Staples","year":"2008","journal-title":"Clin Exp Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2019-002253","article-title":"Ataxia Telangiectasia: What the Neurologist Needs to Know","volume":"20","author":"Tiet","year":"2020","journal-title":"Pract Neurol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.03.052","article-title":"Morbidity and Mortality From Ataxia-Telangiectasia Are Associated With ATM Genotype","volume":"128","author":"Micol","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27319","article-title":"Ataxia-Telangiectasia: A Review of Movement Disorders, Clinical Features, and Genotype Correlations","volume":"33","author":"Levy","year":"2018","journal-title":"Mov Disord Off J Mov Disord Soc"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S295486","article-title":"Multidisciplinary Management of Ataxia Telangiectasia: Current Perspectives","volume":"14","author":"McGrath-Morrow","year":"2021","journal-title":"J Multidiscip Healthc"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13424","article-title":"Ataxia-Telangiectasia: Recommendations for Multidisciplinary Treatment","volume":"59","author":"van Os","year":"2017","journal-title":"Dev Med Child Neurol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28313","article-title":"Assessment of Ataxia Rating Scales and Cerebellar Functional Tests: Critique and Recommendations","volume":"36","author":"Perez-Lloret","year":"2021","journal-title":"Mov Disord Off J Mov Disord Soc"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(97)70200-2","article-title":"Immunophenotyping of Blood Lymphocytes in Childhood. Reference Values for Lymphocyte Subpopulations","volume":"130","author":"Comans-Bitter","year":"1997","journal-title":"J Pediatr"},{"key":"B18","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.jpeds.2011.02.005","article-title":"Neurologic Presentation in Children With Ataxia-Telangiectasia: Is Small Head Circumference a Hallmark of the Disease","volume":"159","author":"Nissenkorn","year":"2011","journal-title":"J Pediatr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12262","article-title":"Immune Deficiency in Ataxia-Telangiectasia: A Longitudinal Study of 44 Patients","volume":"176","author":"Chopra","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.12.046","article-title":"Immunodeficiency and Infections in Ataxia-Telangiectasia","volume":"144","author":"Nowak-Wegrzyn","year":"2004","journal-title":"J Pediatr"},{"key":"B21","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","article-title":"Ataxia Telangiectasia: A Review","volume":"11","author":"Rothblum-Oviatt","year":"2016","journal-title":"Orphanet J Rare Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61870","article-title":"Evidence of Pathogenicity for the Leaky Splice Variant C.1066-6T>G in ATM","volume":"182","author":"Schroder","year":"2020","journal-title":"Am J Med Genet A"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.791522\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T06:50:29Z","timestamp":1643352629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.791522\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":22,"alternative-id":["10.3389\/fimmu.2022.791522"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.791522","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]},"article-number":"791522"}}