{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:10:08Z","timestamp":1788930608337,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We report a 9\u2010year\u2010old female with\n                    <jats:italic>FOXP1<\/jats:italic>\n                    syndrome due to a de novo in\u2010frame deletion in the\n                    <jats:italic>FOXP1<\/jats:italic>\n                    gene. The child has a severe neurodevelopmental disorder including global developmental delay and autism spectrum disorder. At age 2, she developed severe headbanging, which was progressive and did not respond to multidisciplinary, behavioral management strategies or to multiple medication treatments. Although repetitive behaviors are frequent in patients with\n                    <jats:italic>FOXP1<\/jats:italic>\n                    variants, severe and intractable headbanging has not been reported to date. Levodopa\/carbidopa was prescribed at age 7 due to progressive foot dystonia and contracture development. This treatment was not clearly beneficial for the dystonia and foot position, but immediate improvement in headbanging was observed and the response sustained for over 19\u2009months. The\n                    <jats:italic>FOXP1<\/jats:italic>\n                    gene codes for a transcriptional regulator protein that has been shown to regulate the development of brain and spinal motor neurons, and some evidence has linked\n                    <jats:italic>FOXP1<\/jats:italic>\n                    to the differentiation of midbrain dopaminergic neurons via the homeobox protein PITX3, thus providing a potential mechanism for the observed benefit. This case report may provide expansion of the behavioral phenotype associated with\n                    <jats:italic>FOXP1<\/jats:italic>\n                    variants and suggests avenues for further animal research and\/or clinical trial of levodopa in individuals with\n                    <jats:italic>FOXP1<\/jats:italic>\n                    variants.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70303","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:57:51Z","timestamp":1788929871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe Headbanging Responsive to Levodopa in a Child With\n                    <scp>FOXP1<\/scp>\n                    Syndrome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4175-068X","authenticated-orcid":false,"given":"Pamela","family":"Veale","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1674-7330","authenticated-orcid":false,"given":"Christopher","family":"Tiessen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Schulich School of Engineering University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-938X","authenticated-orcid":false,"given":"Vithya","family":"Gnanakumar","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Pediatrics, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"5","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2024.114257","article-title":"Compensation Between FOXP Transcription Factors Maintains Proper Striatal Function","volume":"43","author":"Ahmed N. I.","year":"2024","journal-title":"Cell Reports"},{"issue":"5","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/mp.2014.116","article-title":"Brain\u2010Specific Foxp1 Deletion Impairs Neuronal Development and Causes Autistic\u2010Like Behaviour","volume":"20","author":"Bacon C.","year":"2015","journal-title":"Molecular Psychiatry"},{"issue":"2","key":"e_1_2_11_4_1","first-page":"110","article-title":"Clonidine as a Treatment of Behavioural Disturbances in Autism Spectrum Disorder: A Systematic Literature Review","volume":"29","author":"Banas K.","year":"2020","journal-title":"Journal of the Canadian Academy of Child and Adolescent Psychiatry"},{"issue":"2","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/18758894251323784","article-title":"Gait Abnormalities in Children With FOXP1 Syndrome: A Case Series","volume":"18","author":"Breij L. M.","year":"2025","journal-title":"Journal of Pediatric Rehabilitation Medicine"},{"issue":"2","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/YCO.0000000000000388","article-title":"Lesch\u2010Nyhan Syndrome and Its Variants: Examining the Behavioral and Neurocognitive Phenotype","volume":"31","author":"Harris J. C.","year":"2018","journal-title":"Current Opinion in Psychiatry"},{"issue":"6","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1038\/s41380-020-00995-x","article-title":"FOXP1 Negatively Regulates Intrinsic Excitability in D2 Striatal Projection Neurons by Promoting Inwardly Rectifying and Leak Potassium Currents","volume":"26","author":"Khandelwal N.","year":"2021","journal-title":"Molecular Psychiatry"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adm7039","article-title":"FOXP1 Regulates the Development of Excitatory Synaptic Inputs Onto Striatal Neurons and Induces Phenotypic Reversal With Reinstatement","volume":"10","author":"Khandelwal N.","year":"2024","journal-title":"Science Advances"},{"issue":"4","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/jmg-2023-109537","article-title":"Clinical Phenotype of FOXP1 Syndrome: Parent\u2010Reported Medical Signs and Symptoms in 40 Individuals","volume":"61","author":"Koene S.","year":"2024","journal-title":"Journal of Medical Genetics"},{"issue":"4","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1111\/j.1471-4159.2010.06650.x","article-title":"FoxP1 Promotes Midbrain Identity in Embryonic Stem Cell\u2010Derived Dopamine Neurons by Regulating Pitx3","volume":"113","author":"Konstantoulas C. J.","year":"2010","journal-title":"Journal of Neurochemistry"},{"issue":"12","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1002\/ajmg.a.36174","article-title":"FOXP1 Mutations Cause Intellectual Disability and a Recognizable Phenotype","volume":"161","author":"Le Fevre A. K.","year":"2013","journal-title":"American Journal of Medical Genetics. Part A"},{"issue":"9680","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/S0140-6736(09)60492-X","article-title":"Parkinson's Disease","volume":"373","author":"Lees A. J.","year":"2009","journal-title":"Lancet"},{"issue":"2","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1128\/MCB.24.2.809-822.2004","article-title":"Transcriptional and DNA Binding Activity of the Foxp1\/2\/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions","volume":"24","author":"Li S.","year":"2004","journal-title":"Molecular and Cellular Biology"},{"issue":"1","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s11689-021-09358-1","article-title":"FOXP1 Syndrome: A Review of the Literature and Practice Parameters for Medical Assessment and Monitoring","volume":"13","author":"Lozano R.","year":"2021","journal-title":"Journal of Neurodevelopmental Disorders"},{"key":"e_1_2_11_15_1","first-page":"377","article-title":"Dopa\u2010Responsive Dystonia","volume":"50","author":"Nygaard T. G.","year":"1988","journal-title":"Advances in Neurology"},{"issue":"2","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ejmg.2009.03.012","article-title":"A 785\u2009kb Deletion of 3p14.1p13, Including the FOXP1 Gene, Associated With Speech Delay, Contractures, Hypertonia and Blepharophimosis","volume":"52","author":"Pariani M. J.","year":"2009","journal-title":"European Journal of Medical Genetics"},{"issue":"11","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","DOI":"10.1002\/ajmg.a.63713","article-title":"Joint Contractures Is a Recurrent Clinical Feature of Individuals With Neurodevelopmental Disorder due to FOXP1 Likely Gene Disruptive Variants","volume":"194","author":"Peduto C.","year":"2024","journal-title":"American Journal of Medical Genetics. Part A"},{"issue":"2","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s12031-014-0359-7","article-title":"Transcriptional Regulation by FOXP1, FOXP2, and FOXP4 Dimerization","volume":"55","author":"Sin C.","year":"2015","journal-title":"Journal of Molecular Neuroscience"},{"issue":"1","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jns.2012.02.025","article-title":"Meta\u2010Analysis of Association Between PITX3 Gene Polymorphism and Parkinson's Disease","volume":"317","author":"Tang L.","year":"2012","journal-title":"Journal of the Neurological Sciences"},{"issue":"1","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13229-021-00469-z","article-title":"Individuals With FOXP1 Syndrome Present With a Complex Neurobehavioral Profile With High Rates of ADHD, Anxiety, Repetitive Behaviors, and Sensory Symptoms","volume":"12","author":"Trelles M. P.","year":"2021","journal-title":"Molecular Autism"},{"issue":"4","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/mds.23478","article-title":"Levodopa Is Not a Useful Treatment for Lesch\u2010Nyhan Disease","volume":"26","author":"Visser J.","year":"2011","journal-title":"Movement Disorders"},{"key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pediatrneurol.2024.03.020","article-title":"Very Early Levodopa May Prevent Self\u2010Injury in Lesch\u2010Nyhan Disease","volume":"155","author":"Visser J. E.","year":"2024","journal-title":"Pediatric Neurology"},{"issue":"7","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nrneurol.2015.86","article-title":"Dopa\u2010Responsive Dystonia\u2014Clinical and Genetic Heterogeneity","volume":"11","author":"Wijemanne S.","year":"2015","journal-title":"Nature Reviews. Neurology"},{"issue":"5","key":"e_1_2_11_24_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26051938","article-title":"Molecular Pathways, Neural Circuits and Emerging Therapies for Self\u2010Injurious Behaviour","volume":"26","author":"Zhang K.","year":"2025","journal-title":"International Journal of Molecular Sciences"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70303","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70303","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:57:55Z","timestamp":1788929875000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":23,"alternative-id":["10.1002\/ajmg.a.70303"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70303","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"assertion":[{"value":"2026-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70303"}}