{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:01:49Z","timestamp":1787241709554,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"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. Pediatr."],"abstract":"<jats:p>\n                    Andersen\u2013Tawil syndrome (ATS) is a rare autosomal dominant disorder characterized by a classic symptom triad: periodic paralysis, ventricular arrhythmias associated with prolonged QT interval, and dysmorphic skeletal and facial features. Pathogenic variants of the inwardly rectifying potassium channel subfamily J member 2 (KCNJ2) gene have been linked to the ATS. Herein, we report a novel\n                    <jats:italic>KCNJ2<\/jats:italic>\n                    causative variant in a proband and her father showing different ATS-associated symptoms. A 15-year-old girl was referred because of episodic weakness and periodic paralysis in both legs for 2\u20133 months. The symptoms occurred either when she was tired or after strenuous exercise. These attacks made walking or climbing stairs difficult and lasted from one to several days. She had a short stature (142 cm, &amp;lt;3rd percentile) and weighed 40 kg. The proband also showed orbital hypertelorism, dental crowding, mandibular hypoplasia, fifth-digit clinodactyly, and small hands. Scoliosis in the thoracolumbar region was detected by chest X-ray. Since she was 7 years old, she had been treated for arrhythmia-associated long QT interval and underwent periodic echocardiography. Brain MRI revealed cerebrovascular abnormalities indicating absence or hypoplasia of bilateral internal carotid arteries, and compensation of other collateral vessels was observed. There were no specific findings related to intellectual development. The proband's father also had a history of periodic paralysis similar to the proband. He did not show any cardiac symptoms. Interestingly, he was diagnosed with hyperthyroidism during an evaluation for paralytic symptoms. Clinical exome sequencing revealed a novel heterozygous missense variant: Chr17(GRCh37):g.68171593A&amp;gt;T, NM_000891.2:c.413A&amp;gt;T, p.(Glu138Val) in\n                    <jats:italic>KCNJ2<\/jats:italic>\n                    in the proband and the proband's father.\n                  <\/jats:p>","DOI":"10.3389\/fped.2021.790075","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T10:46:16Z","timestamp":1643625976000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Andersen\u2013Tawil Syndrome With Novel Mutation in KCNJ2: Case Report"],"prefix":"10.3389","volume":"9","author":[{"given":"Jisook","family":"Yim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Bo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Dong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myungshin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"B1","unstructured":"Andersen-Tawil syndrome\n            VeerapandiyanA\n            StatlandJM\n            TawilR\n          \n            AdamMP\n            ArdingerHH\n            PagonRA\n            WallaceSE\n            BeanLJH\n            MirzaaG\n            AmemiyaA\n          Seattle (WA)GeneReviews1993"},{"key":"B2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1111\/j.1651-2227.1971.tb06990.x","article-title":"Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome?","volume":"60","author":"Andersen","year":"1971","journal-title":"Acta Paediatr Scand."},{"key":"B3","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.nmd.2018.03.006","article-title":"Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands","volume":"28","author":"Stunnenberg","year":"2018","journal-title":"Neuromuscul Disord."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1212\/WNL.0b013e31828cf8d0","article-title":"Prevalence study of genetically defined skeletal muscle channelopathies in England","volume":"80","author":"Horga","year":"2013","journal-title":"Neurology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijcard.2013.10.010","article-title":"Andersen-Tawil syndrome: clinical and molecular aspects","volume":"170","author":"Nguyen","year":"2013","journal-title":"Int J Cardiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1097\/CRD.0000000000000326","article-title":"Andersen-Tawil syndrome: a comprehensive review","volume":"29","author":"Perez-Riera","year":"2021","journal-title":"Cardiol Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/ajmg.a.31092","article-title":"Andersen-Tawil syndrome: prospective cohort analysis and expansion of the phenotype","volume":"140","author":"Yoon","year":"2006","journal-title":"Am J Med Genet A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S0092-8674(01)00342-7","article-title":"Mutations in Kir21 cause the developmental and episodic electrical phenotypes of Andersen's syndrome","volume":"105","author":"Plaster","year":"2001","journal-title":"Cell."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1212\/WNL.0000000000000239","article-title":"A Kir34 mutation causes Andersen-Tawil syndrome by an inhibitory effect on Kir21","volume":"82","author":"Kokunai","year":"2014","journal-title":"Neurology."},{"key":"B10","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1002\/mus.24293","article-title":"Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement","volume":"51","author":"Kostera-Pruszczyk","year":"2015","journal-title":"Muscle Nerve."},{"key":"B11","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/mus.26009","article-title":"Review of the diagnosis and treatment of periodic paralysis","volume":"57","author":"Statland","year":"2018","journal-title":"Muscle Nerve."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e78","DOI":"10.1212\/WNL.0000000000001377","article-title":"Child neurology: Andersen-Tawil syndrome","volume":"84","author":"Almuqbil","year":"2015","journal-title":"Neurology."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.3390\/cells10061521","article-title":"Ion channel gene mutations causing skeletal muscle disorders: pathomechanisms and opportunities for therapy","volume":"10","author":"Maggi","year":"2021","journal-title":"Cells"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.1113\/JP271930","article-title":"Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2-associated Andersen-Tawil Syndrome","volume":"594","author":"Adams","year":"2016","journal-title":"J Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1086\/342360","article-title":"KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes","volume":"71","author":"Andelfinger","year":"2002","journal-title":"Am J Hum Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e284","DOI":"10.1212\/NXG.0000000000000284","article-title":"Variable penetrance of Andersen-Tawil syndrome in a family with a rare missense KCNJ2 mutation","volume":"4","author":"Deeb","year":"2018","journal-title":"Neurol Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1172\/JCI15183","article-title":"Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)","volume":"110","author":"Tristani-Firouzi","year":"2002","journal-title":"J Clin 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Defective potassium channel Kir21 trafficking underlies Andersen-Tawil syndrome","volume":"278","author":"Bendahhou","year":"2003","journal-title":"J Biol Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"145","DOI":"10.24875\/RIC.20000310","article-title":"Andersen-Tawil syndrome with high risk of sudden cardiac death in four mexican patients. Cardiac and extra-cardiac phenotypes","volume":"73","author":"Barron-Diaz","year":"2021","journal-title":"Rev Invest Clin."},{"key":"B22","doi-asserted-by":"publisher","first-page":"650","DOI":"10.3390\/biom9110650","article-title":"Disease associated mutations in KIR proteins linked to aberrant inward rectifier channel trafficking","volume":"9","author":"Zangerl-Plessl","year":"2019","journal-title":"Biomolecules."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1073\/pnas.94.4.1568","article-title":"Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel","volume":"94","author":"Yang","year":"1997","journal-title":"Proc Natl Acad Sci USA."},{"key":"B24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1124\/jpet.114.222000","article-title":"ATP-sensitive potassium channel activation induces angiogenesis in vitro and in vivo","volume":"354","author":"Umaru","year":"2015","journal-title":"J Pharmacol Exp Ther"},{"key":"B25","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/jhg.2014.43","article-title":"Severe exacerbation of Andersen-Tawil syndrome secondary to thyrotoxicosis","volume":"59","author":"Diaz-Manera","year":"2014","journal-title":"J Hum Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e8169","DOI":"10.7759\/cureus.8169","article-title":"Thyrotoxic periodic paralysis with features of Andersen-Tawil syndrome: a case report and literature review","volume":"12","author":"Iskander","year":"2020","journal-title":"Cureus."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.790075\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T10:46:18Z","timestamp":1643625978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.790075\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,31]]},"references-count":26,"alternative-id":["10.3389\/fped.2021.790075"],"URL":"https:\/\/doi.org\/10.3389\/fped.2021.790075","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,31]]},"article-number":"790075"}}