{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:35Z","timestamp":1791928955902,"version":"4.3.4"},"reference-count":20,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">SLC6A1<\/jats:italic>\n                    -related neurodevelopmental disorder is a synaptopathy characterized by developmental delay, epilepsy, and neurobehavioral manifestations with marked phenotypic variability. Variants impair \u03b3-aminobutyric acid (GABA) transporter-1 (GAT-1) folding and trafficking, reducing inhibitory neurotransmission and promoting hyperexcitability. Pharmacologic chaperones such as 4-phenylbutyrate (4-PBA) may restore GAT-1 function. We report a 3-generation family harboring a heterozygous\n                    <jats:italic toggle=\"yes\">SLC6A1<\/jats:italic>\n                    variant with segregating neurodevelopmental and epileptic phenotypes. The proband presented with drug-resistant developmental and epileptic encephalopathy, multiple seizure types, diffuse epileptiform abnormalities, and global developmental delay. Segregation analysis demonstrated co-segregation of the variant with epilepsy and neurodevelopmental features across affected relatives. Because of persistent seizures despite antiseizure medications, glycerol phenylbutyrate (GPB), a prodrug of 4-PBA, was initiated, resulting in complete seizure freedom and reduction of epileptiform discharges on follow-up electroencephalography. These findings highlight the potential role of genotype-informed precision therapy in\n                    <jats:italic toggle=\"yes\">SLC6A1<\/jats:italic>\n                    -related disorders and underscore the importance of careful variant interpretation in familial cases.\n                  <\/jats:p>","DOI":"10.1177\/08830738261484306","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T17:17:27Z","timestamp":1789233447000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenylbutyrate-Responsive\n                    <i>SLC6A1<\/i>\n                    -Related Neurodevelopmental Disorder Associated With a Familial Variant"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5890-2057","authenticated-orcid":false,"given":"Odette El","family":"Ghawi","sequence":"first","affiliation":[{"name":"Neurosurgery, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniya","family":"Beemarajan","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-8717","authenticated-orcid":false,"given":"Debopam","family":"Samanta","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0165-6955","authenticated-orcid":false,"given":"Praveen Kumar","family":"Ramani","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa371"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac144"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1289821"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.02.016"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1026065"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gimo.2025.102276"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1219262"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13986"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.6027767"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa170"},{"key":"e_1_3_3_12_2","volume-title":"GeneReviews\u00ae","author":"Goodspeed K","year":"1993","unstructured":"Goodspeed K, Demarest S, Johannesen K, Kang J, Lal D, Angione K. SLC6A1-related neurodevelopmental disorder. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews\u00ae. University of Washington; 1993. Accessed April 25, 2026. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK589173\/"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2025.107621"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2025.107514"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","unstructured":"Grinspan ZM Burr\u00e9 J Cross J et al. 4-Phenylbutyrate for STXBP1 and SLC6A1. Safety tolerability seizure and EEG outcomes. A case series at 2 centers. medRxiv. Preprint posted online November 10 2024:2024.11.06.24316676. doi:10.1101\/2024.11.06.24316676","DOI":"10.1101\/2024.11.06.24316676"},{"key":"e_1_3_3_16_2","unstructured":"Clinical experiences using phenylbutyrate off-label for stxbp1 and slc6a1 [abstract]. Accessed May 15 2026. https:\/\/aesnet.org\/abstractslisting\/clinical-experiences-using-phenylbutyrate-off-label-for-stxbp1-and-slc6a1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-00612-6"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","unstructured":"Crunelli V L\u0151rincz ML McCafferty C et al. Clinical and experimental insight into pathophysiology comorbidity and therapy of absence seizures. Brain. 2020;143(8):2341-2368. doi:10.1093\/brain\/awaa072","DOI":"10.1093\/brain\/awaa072"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17779"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2024.1466694"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.03.015"}],"container-title":["Journal of Child Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08830738261484306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/08830738261484306","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08830738261484306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:47:56Z","timestamp":1789408076000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/08830738261484306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":20,"alternative-id":["10.1177\/08830738261484306"],"URL":"https:\/\/doi.org\/10.1177\/08830738261484306","relation":{},"ISSN":["0883-0738","1708-8283"],"issn-type":[{"value":"0883-0738","type":"print"},{"value":"1708-8283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]},"article-number":"08830738261484306"}}