{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:16:59Z","timestamp":1787912219466,"version":"build-2784847793"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008908","name":"Universit\u00e0 degli Studi di Messina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008908","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mutations in the ACTL6B gene are implicated in a wide range of neurodevelopmental disorders, such as global developmental delay, drug-resistant epilepsy, aphasia, autistic traits, dystonia, and cerebral malformations. Recessive variants are typically associated with severe phenotypes, while dominant mutations lead to moderate-to-severe clinical presentations. Although neurological involvement is well characterized, gastrointestinal manifestations, particularly motility disorders, have not been previously associated with ACTL6B-related disease. Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare, severe gastrointestinal dysmotility disorder. Pyridostigmine, an acetylcholinesterase inhibitor with prokinetic effects, has recently been used off-label in selected PIPO cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We present the clinical course of a 9-year-old female patient with a confirmed pathogenic ACTL6B mutation and a severe neurodevelopmental phenotype. Following persistent feeding intolerance and failure to thrive, the patient underwent surgical intervention, which did not result in significant clinical improvement. Given the suspected neuropathic component of the gastrointestinal dysmotility, pyridostigmine therapy was initiated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The introduction of pyridostigmine led to improved enteral feeding tolerance, a marked reduction in vomiting episodes, and stabilization of nutritional status, suggesting a potential benefit in managing gastrointestinal symptoms in this patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This case suggests a possible link between ACTL6B-related neurodevelopmental disorders and gastrointestinal dysmotility; if confirmed, it could expand the known clinical spectrum of the disease. Pyridostigmine could be considered as adjunctive therapy in PIPO, especially when a neuropathic etiology is suspected.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1761705","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:36:22Z","timestamp":1776922582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential role of pyridostigmine in the management of pediatric chronic intestinal pseudo-obstruction in a girl with ACTL6B mutation: a case report and a review of literature"],"prefix":"10.3389","volume":"14","author":[{"given":"Immacolata","family":"Rulli","sequence":"first","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Mattia","family":"Carcione","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Romano","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Chimenz","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology and Dialysis Unit, Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Chirico","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology and Dialysis Unit, Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Marseglia","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Romeo","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Unit, Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloisa","family":"Gitto","sequence":"additional","affiliation":[{"name":"Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1097\/MPG.0000000000001982","article-title":"Paediatric intestinal pseudo-obstruction: evidence and consensus-based recommendations from an ESPGHAN-led expert group","volume":"66","author":"Thapar","year":"2018","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1007\/s00431-021-04365-9","article-title":"Paediatric intestinal pseudo-obstruction: a scoping review","volume":"181","author":"Nham","year":"2022","journal-title":"Eur J Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s11894-019-0737-y","article-title":"Pediatric intestinal pseudo-obstruction in the era of genetic sequencing","volume":"21","author":"Gamboa","year":"2019","journal-title":"Curr Gastroenterol Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1542\/pir.2024-006523","article-title":"Pediatric intestinal pseudo-obstruction: a review","volume":"46","author":"Gandhi","year":"2025","journal-title":"Pediatr Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e14259","DOI":"10.1111\/nmo.14259","article-title":"Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction","volume":"34","author":"Chanpong","year":"2022","journal-title":"Neurogastroenterol Motil"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e14562","DOI":"10.1111\/nmo.14562","article-title":"Optimizing nutrition in pediatric intestinal pseudo-obstruction syndrome","volume":"35","author":"Pescarin","year":"2023","journal-title":"Neurogastroenterol Motil"},{"key":"B7","doi-asserted-by":"publisher","first-page":"596","DOI":"10.5152\/tjg.2020.19233","article-title":"Challenges in management and prognosis of pediatric intestinal pseudo-obstruction","volume":"31","author":"Boybeyi T\u00fcrer","year":"2020","journal-title":"Turk J Gastroenterol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"837462","DOI":"10.3389\/fped.2022.837462","article-title":"Pediatric intestinal pseudo-obstruction: progress and challenges","volume":"10","author":"Turcotte","year":"2022","journal-title":"Front Pediatr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"111174","DOI":"10.1016\/j.nut.2021.111174","article-title":"Percutaneous endoscopic gastrojejunostomy in pediatric intestinal pseudo-obstruction","volume":"86","author":"Di Nardo","year":"2021","journal-title":"Nutrition"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.3390\/jcm10112376","article-title":"Clinical outcomes of pediatric chronic intestinal pseudo-obstruction","volume":"10","author":"Ko","year":"2021","journal-title":"J Clin Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/ncp.10929","article-title":"Long-term follow-up for pediatric intestinal pseudo-obstruction patients in China","volume":"38","author":"Tang","year":"2023","journal-title":"Nutr Clin Pract"},{"key":"B12","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1097\/MPG.0000000000002373","article-title":"Pediatric intestinal pseudo-obstruction: impact of neonatal and later onset on clinical and nutritional outcomes","volume":"69","author":"Diamanti","year":"2019","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1056\/NEJMra1602678","article-title":"Myasthenia gravis","volume":"375","author":"Gilhus","year":"2016","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"691","DOI":"10.2165\/11593300-000000000-00000","article-title":"Treatment of myasthenia gravis: focus on pyridostigmine","volume":"31","author":"Maggi","year":"2011","journal-title":"Clin Drug Investig"},{"key":"B15","doi-asserted-by":"publisher","first-page":"101251","DOI":"10.1016\/j.gim.2024.101251","article-title":"Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders","volume":"27","author":"Cali","year":"2025","journal-title":"Genet Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.ajhg.2019.03.022","article-title":"Mutations in ACTL6B cause neurodevelopmental deficits and epilepsy and lead to loss of dendrites in human neurons","volume":"104","author":"Bell","year":"2019","journal-title":"Am J Hum Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s00439-019-01972-3","article-title":"Mutations in ACTL6B, coding for a subunit of the neuron-specific chromatin remodeling complex nBAF, cause early onset severe developmental and epileptic encephalopathy with brain hypomyelination and cerebellar atrophy","volume":"138","author":"Fichera","year":"2019","journal-title":"Hum Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1002\/ajmg.a.61210","article-title":"Pathogenic homozygous variations in ACTL6B cause DECAM syndrome: developmental delay, epileptic encephalopathy, cerebral atrophy, and abnormal myelination","volume":"179","author":"Y\u00fcksel","year":"2019","journal-title":"Am J Med Genet A"},{"key":"B19","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/jnr.24747","article-title":"An epilepsy-associated ACTL6B variant captures neuronal hyperexcitability in a human induced pluripotent stem cell model","volume":"99","author":"Ahn","year":"2021","journal-title":"J Neurosci Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"10055","DOI":"10.1073\/pnas.1908238117","article-title":"Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes and causes recessive autism","volume":"117","author":"Wenderski","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B21","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.nmd.2022.09.002","article-title":"The effectiveness and side effects of pyridostigmine in the treatment of myasthenia gravis: a cross-sectional study","volume":"32","author":"Remijn-Nelissen","year":"2022","journal-title":"Neuromuscul Disord"},{"key":"B22","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1136\/gutjnl-2012-302483","article-title":"A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation","volume":"62","author":"Bharucha","year":"2013","journal-title":"Gut"},{"key":"B23","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s10286-008-0476-x","article-title":"Pilot study of pyridostigmine in constipated patients with autonomic neuropathy","volume":"18","author":"Bharucha","year":"2008","journal-title":"Clin Auton Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e13948","DOI":"10.1111\/nmo.13948","article-title":"Colonic motility in patients with type 1 diabetes and gastrointestinal symptoms","volume":"32","author":"Klinge","year":"2020","journal-title":"Neurogastroenterol Motil"},{"key":"B25","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.semarthrit.2017.12.007","article-title":"Pyridostigmine for the treatment of gastrointestinal symptoms in systemic sclerosis","volume":"48","author":"Ahuja","year":"2018","journal-title":"Semin Arthritis Rheum"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1111\/codi.15748","article-title":"PyRICo-Pilot: Pyridostigmine to reduce the duration of postoperative ileus after colorectal surgery - A phase II study","volume":"23","author":"Dudi-Venkata","year":"2021","journal-title":"Colorectal Dis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3390\/jcm7050104","article-title":"Evaluation of the effect of oral pyridostigmine on the ileus after abdominal surgery: a blinded randomized clinical trial","volume":"7","author":"Maleknejad","year":"2018","journal-title":"J Clin Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"S404","DOI":"10.1542\/peds.2017-0007","article-title":"The use of pyridostigmine in a child with chronic intestinal Pseudo-obstruction","volume":"141","author":"Choudhury","year":"2018","journal-title":"Pediatrics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"508","DOI":"10.5056\/jnm19078","article-title":"Pyridostigmine in pediatric intestinal pseudo- obstruction: case report of a 2-year-old girl and literature review","volume":"25","author":"Di Nardo","year":"2019","journal-title":"J Neurogastroenterol Motil"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1097\/MPG.0000000000002183","article-title":"Oral pyridostigmine-responsive visceral myopathy with ACTG2 mutations: a case series","volume":"68","author":"Lee","year":"2019","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s40272-017-0277-6","article-title":"Application of pyridostigmine in pediatric gastrointestinal motility disorders: a case series","volume":"20","author":"Manini","year":"2018","journal-title":"Paediatr Drugs"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.1111\/ans.18478","article-title":"Pyridostigmine in chronic intestinal pseudo-obstruction\u2014a systematic review","volume":"93","author":"Wilkie","year":"2023","journal-title":"ANZ J Surg"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1460658","DOI":"10.3389\/fped.2024.1460658","article-title":"Pyridostigmine as a therapeutic option for pediatric gastrointestinal dysmotilities in ATR-X syndrome. Case report and literature review","volume":"12","author":"Comisi","year":"2024","journal-title":"Front Pediatr"}],"updated-by":[{"DOI":"10.3389\/fped.2026.1958105","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000}}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1761705\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:26:16Z","timestamp":1787909176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1761705\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":33,"alternative-id":["10.3389\/fped.2026.1761705"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1761705","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"article-number":"1761705"}}