{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:21:31Z","timestamp":1789269691612,"version":"build-2803163510"},"reference-count":31,"publisher":"Elsevier BV","issue":"02","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glob Med Genet"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Idiopathic toe walking (ITW) describes a condition affecting approximately 4.5% of children. Toe walking is an accompanying symptom for many hereditary disorders. This retrospective study uses next-generation sequencing-panel-diagnosis to investigate the feasibility of genetic testing to research the possible genetic causes of ITW and for differential diagnosis.<\/jats:p><jats:p>Data were taken from our inhouse database, the minimum age for participants was 3 years. Underlying neurological or orthopaedic conditions were tested for and ruled out prior to diagnosing ITW. Patients, who experienced complications before, during or immediately after birth, children with autism, and patients toe walking less than 50% of the time were excluded.<\/jats:p><jats:p>Eighty-nine patients were included in the study, in which 66 (74.2%) patients were boys and 23 (25.8%) girls. Mean age at testing was 7.7 years (range: 3\u201317 years). Fifteen of the 89 patients included in the study (16.9%) had a genetic variant identified as likely pathogenic or pathogenic by the genetics laboratory. Additionally, we found 129 variants of uncertain significance. About 65.2% of patients showed a pes cavus foot deformity, 27% of patients reportedly had at least one relative who also displayed the gait anomaly, and 37.1% had problems with their speech development.<\/jats:p><jats:p>Despite the limitations of the sample size and the scope of our genetic testing targets, our results indicate that research into the genetic causes of ITW could better our understanding of the causes of ITW in otherwise healthy children, to help develop novel methods to detect serious conditions early. ITW could be an early onset symptom for further hereditary conditions.<\/jats:p>","DOI":"10.1055\/s-0043-57230","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T23:42:03Z","timestamp":1682120523000},"page":"063-071","source":"Crossref","is-referenced-by-count":7,"title":["NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly"],"prefix":"10.1016","volume":"10","author":[{"given":"David","family":"Pomarino","sequence":"additional","affiliation":[{"name":"Praxis Pomarino, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Emelina","sequence":"additional","affiliation":[{"name":"Praxis Pomarino, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Heidrich","sequence":"additional","affiliation":[{"name":"Labor Dr. Heidrich und Kollegen MVZ GmbH, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Rost\u00e1sy","sequence":"additional","affiliation":[{"name":"Kinderklinik Datteln, Datteln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Schirmer","sequence":"additional","affiliation":[{"name":"SANA Klinikum Offenbach, Offenbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan O.","family":"Sch\u00f6nfeldt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Kinderneurologie, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"Thren","sequence":"additional","affiliation":[{"name":"Kinderorthop\u00e4die am Pferdeturm, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, Musculoskeletal University Center Munich, University Hospital, Ludwig-Maximilians-University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna Ronja","family":"Thren","sequence":"additional","affiliation":[{"name":"Anthropology Department, Durham University, Durham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Berger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Kinderneurologie, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"issue":"10","key":"ref1","first-page":"CD012363","article-title":"Interventions for idiopathic toe walking","volume":"10","author":"A J Caserta","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1302\/0301-620X.49B4.695","article-title":"Congenital short tendo calcaneus","volume":"49","author":"J E Hall","year":"1967","journal-title":"J Bone Joint Surg Br"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.gaitpost.2010.07.011","article-title":"The toe walking tool: a novel method for assessing idiopathic toe walking children","volume":"32","author":"C M Williams","year":"2010","journal-title":"Gait Posture"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1757-1146-3-16","article-title":"Idiopathic toe walking and sensory processing dysfunction","volume":"3","author":"C M Williams","year":"2010","journal-title":"J Foot Ankle Res"},{"issue":"03","key":"ref5","doi-asserted-by":"crossref","first-page":"253","DOI":"10.7547\/0003-0538-104.3.253","article-title":"Idiopathic toe-walking: have we progressed in our knowledge of the causality and treatment of this gait type?","volume":"104","author":"C M Williams","year":"2014","journal-title":"J Am Podiatr Med Assoc"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S1090-3798(99)90982-0","article-title":"Influence of infant-walkers on motor development: mimicking spastic diplegia?","volume":"3","author":"R H Engelbert","year":"1999","journal-title":"Eur J Paediatr Neurol"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"640","DOI":"10.2106\/JBJS.17.00851","article-title":"Idiopathic toe-walking: prevalence and natural history from birth to ten years of age","volume":"100","author":"P Engstr\u00f6m","year":"2018","journal-title":"J Bone Joint Surg Am"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1001\/archpedi.1973.04160060062014","article-title":"Congenital short tendo calcaneus. Report of a family","volume":"125","author":"M S Levine","year":"1973","journal-title":"Am J Dis Child"},{"issue":"06","key":"ref9","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/01241398-198411000-00011","article-title":"Hereditary tendon Achilles contractures","volume":"4","author":"M M Katz","year":"1984","journal-title":"J Pediatr Orthop"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1542\/peds.2012-0225","article-title":"The prevalence and course of idiopathic toe-walking in 5-year-old children","volume":"130","author":"P Engstr\u00f6m","year":"2012","journal-title":"Pediatrics"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/01241398-198601000-00006","article-title":"Electromyography of idiopathic toe walking","volume":"6","author":"V Kalen","year":"1986","journal-title":"J Pediatr Orthop"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0022-3476(97)70236-1","article-title":"Developmental implications of idiopathic toe walking","volume":"130","author":"L H Shulman","year":"1997","journal-title":"J Pediatr"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.7547\/87507315-87-1-17","article-title":"Effect of persistent toe walking on ankle equinus. 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Relationship between idiopathic toe-walking and ADHD]","volume":"88","author":"V Soto Insuga","year":"2018","journal-title":"An Pediatr (Engl Ed)"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/01202412-199707000-00012","article-title":"Muscle abnormalities in idiopathic toe-walkers","volume":"6","author":"D M Eastwood","year":"1997","journal-title":"J Pediatr Orthop B"},{"issue":"10","key":"ref20","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/ptj\/58.10.1195","article-title":"Sensory dysfunction in children who toe walk","volume":"58","author":"P Montgomery","year":"1978","journal-title":"Phys Ther"},{"issue":"07","key":"ref21","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1177\/0883073815624760","article-title":"The effects of walking surface on the gait pattern of children with idiopathic toe walking","volume":"31","author":"H D Fanchiang","year":"2016","journal-title":"J Child Neurol"},{"issue":"11","key":"ref22","doi-asserted-by":"crossref","first-page":"967","DOI":"10.5014\/ajot.48.11.967","article-title":"Performance of typical children on the sensory profile: an item analysis","volume":"48","author":"W Dunn","year":"1994","journal-title":"Am J Occup Ther"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1016\/j.otsr.2017.04.019","article-title":"Neuromuscular diseases: diagnosis and management","volume":"104","author":"P Mary","year":"2018","journal-title":"Orthop Traumatol Surg Res"},{"issue":"06","key":"ref24","first-page":"91","article-title":"Hereditary neuropathies","volume":"115","author":"K Eggermann","year":"2018","journal-title":"Dtsch Arztebl Int"},{"issue":"02","key":"ref25","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/jns5.12026","article-title":"Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes","volume":"18","author":"M Tazir","year":"2013","journal-title":"J Peripher Nerv Syst"},{"issue":"14","key":"ref26","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.3390\/ijms20143419","article-title":"Charcot-Marie-Tooth: from molecules to therapy","volume":"20","author":"J Morena","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"03","key":"ref27","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/BPO.0000000000001115","article-title":"Toe walking: a neurological perspective after referral from pediatric orthopaedic surgeons","volume":"38","author":"K B Haynes","year":"2018","journal-title":"J Pediatr Orthop"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"759505","DOI":"10.3389\/fped.2021.759505","article-title":"Myotonia congenita: clinical characteristic and mutation spectrum of CLCN1 in Chinese patients","volume":"9","author":"C Hu","year":"2021","journal-title":"Front Pediatr"},{"issue":"11","key":"ref29","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/humu.20889","article-title":"Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes","volume":"29","author":"M S Greenblatt","year":"2008","journal-title":"Hum Mutat"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"310","DOI":"10.15690\/vsp.v20i4.2287","article-title":"Mutation in the CREBBP gene in the girl with toe walking syndrome: clinical case","volume":"20","author":"D Pomarino","year":"2021","journal-title":"Curr Paediatr"},{"issue":"01","key":"ref31","first-page":"51","article-title":"Toe walking as the initial symptom of a spinocerebellar ataxia 13 in a patient presenting with a mutation in the KCNC3 gene","volume":"9","author":"D Pomarino","year":"2021","journal-title":"Glob Med Genet"}],"container-title":["Global Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-57230.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T15:23:21Z","timestamp":1736436201000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-57230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":31,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2023,4,17]]},"published-print":{"date-parts":[[2023,6]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-57230","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2699-9404"],"issn-type":[{"value":"2699-9404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}