{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:04:34Z","timestamp":1778313874299,"version":"3.51.4"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      X-linked centronuclear myopathy (XLCNM) is a rare congenital neuromuscular disorder caused by pathogenic variants in\n                      <jats:italic>MTM1<\/jats:italic>\n                      , typically presenting with severe neonatal hypotonia, respiratory failure, and poor survival. Early diagnosis is essential for prognosis and genetic counseling, though clinical recognition is often challenging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a male infant, born at 38\u2009+\u20091 weeks via cesarean section, who presented immediately after birth with apnea, cyanosis, hypotonia, and poor responsiveness. Despite resuscitation and intensive care for neonatal asphyxia and sepsis, he remained ventilator-dependent with persistent hypotonia and feeding difficulties. Laboratory evaluation showed anemia of chronic disease, hypoproteinemia, vitamin D insufficiency, and mild hepatic dysfunction. Imaging revealed laryngomalacia and a patent foramen ovale. Given the family history of neonatal death in a male sibling, whole-exome sequencing (WES) was performed and identified a hemizygous nonsense mutation in\n                      <jats:italic>MTM1<\/jats:italic>\n                      (NM_000252.2): c.373C\u2009&amp;gt;\u2009T (p.Gln125Ter), confirming XLCNM. Maternal heterozygosity was verified by Sanger sequencing, consistent with X-linked recessive inheritance. In view of the severe clinical course and poor prognosis, the family declined further treatment. The patient was discharged for palliative care and died shortly after from respiratory failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case reveals the importance of early recognition and genetic diagnosis of XLCNM, particularly in neonates with unexplained hypotonia and a suggestive family history. Through our literature review, we emphasize the need for heightened clinical awareness, summarize current therapeutic and research advances, and discusses supportive strategies that may optimize survival and quality of life in affected infants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1735095","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:26:55Z","timestamp":1774848415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["X-linked myotubular myopathy in a neonate: a case report and literature review"],"prefix":"10.3389","volume":"14","author":[{"given":"Lin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neonatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Qun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/cge.14054","article-title":"Clinical, genetic, and histological features of centronuclear myopathy in The Netherlands","volume":"100","author":"Reumers","year":"2021","journal-title":"Clin Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"339","DOI":"10.3389\/fnagi.2014.00339","article-title":"Pathogenic mechanisms in centronuclear myopathies","volume":"6","author":"Jungbluth","year":"2014","journal-title":"Front Aging Neurosci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1750-1172-3-26","article-title":"Centronuclear (myotubular) myopathy","volume":"3","author":"Jungbluth","year":"2008","journal-title":"Orphanet J Rare Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.nmd.2012.06.136","article-title":"C.P.8 clinical and pathological characterization of sporadic centronuclear myopathy by DNM2 mutations","volume":"22","author":"Park","year":"2012","journal-title":"Neuromuscul Disord"},{"key":"B5","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.nmd.2010.07.273","article-title":"Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutation","volume":"20","author":"Liewluck","year":"2010","journal-title":"Neuromuscul Disord"},{"key":"B6","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1080\/14712598.2025.2473430","article-title":"X-linked myotubular myopathy: an untreated treatable disease","volume":"25","author":"Martin","year":"2025","journal-title":"Expert Opin Biol Ther"},{"key":"B7","doi-asserted-by":"publisher","first-page":"11377","DOI":"10.3390\/ijms222111377","article-title":"Common pathogenic mechanisms in centronuclear and myotubular myopathies and latest treatment advances","volume":"22","author":"Gomez-Oca","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e513","DOI":"10.1212\/NXG.0000000000000513","article-title":"Manifesting carriers of X-linked myotubular myopathy: genetic modifiers modulating the phenotype","volume":"6","author":"Souza","year":"2020","journal-title":"Neurol Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1002\/mus.26018","article-title":"A multicenter, retrospective medical record review of X-linked myotubular myopathy: the recensus study","volume":"57","author":"Beggs","year":"2018","journal-title":"Muscle Nerve"},{"key":"B10","doi-asserted-by":"publisher","first-page":"00641-2020","DOI":"10.1183\/23120541.00641-2020","article-title":"Respiratory care in myotubular myopathy","volume":"7","author":"Tan","year":"2021","journal-title":"ERJ Open Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1136\/archdischild-2019-317910","article-title":"Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis","volume":"105","author":"Graham","year":"2020","journal-title":"Arch Dis Child"},{"key":"B12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3233\/JND-200539","article-title":"Diagnosing X-linked myotubular myopathy\u2014a German 20-year follow up experience","volume":"8","author":"Gangfuss","year":"2020","journal-title":"J Neuromuscul Dis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.nmd.2016.06.115","article-title":"MTM1-related myopathy carrier females manifest significant skeletal asymmetries and a spectrum of muscle involvement","volume":"26","author":"Reghan Foley","year":"2016","journal-title":"Neuromuscul Disord"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion","volume":"39","author":"Abou Tayoun","year":"2018","journal-title":"Hum Mutat"},{"key":"B15","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.pedneo.2024.02.009","article-title":"X-linked myotubular myopathy in a family of two infant siblings: a case report and review","volume":"65","author":"Koe","year":"2024","journal-title":"Pediatr Neonatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"491","DOI":"10.11817\/j.issn.1672-7347.2024.230450","article-title":"Neonatal X-linked myotubular myopathy with a de novo mutation: a case report and literature review","volume":"49","author":"Hu","year":"2024","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"B17","first-page":"812","article-title":"Clinical characteristics and genetic analysis of two children with X-linked centronuclear myopathy due to variants of MTM1 gene","volume":"41","author":"Wang","year":"2024","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B18","doi-asserted-by":"publisher","first-page":"10274","DOI":"10.3390\/ijms231810274","article-title":"Novel splicing mutation in MTM1 leading to two abnormal transcripts causes severe myotubular myopathy","volume":"23","author":"Bosco","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3233\/JND-210712","article-title":"Intrahepatic cholestasis is a clinically significant feature associated with natural history of X-linked myotubular myopathy (XLMTM): a case series and biopsy report","volume":"9","author":"Molera","year":"2022","journal-title":"J Neuromuscul Dis"},{"key":"B20","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.nmd.2021.04.009","article-title":"Intracranial hemorrhage secondary to vitamin K deficiency in X-linked myotubular myopathy","volume":"31","author":"Neese","year":"2021","journal-title":"Neuromuscul Disord"},{"key":"B21","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41431-020-00715-7","article-title":"Pathogenic deep intronic MTM1 variant activates a pseudo-exon encoding a nonsense codon resulting in severe X-linked myotubular myopathy","volume":"29","author":"Bryen","year":"2021","journal-title":"Eur J Hum Genet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e20182879","DOI":"10.1542\/peds.2018-2879","article-title":"X-Linked myotubular myopathy and duchenne muscular dystrophy in a preterm infant: a rare combination","volume":"146","author":"Varma","year":"2020","journal-title":"Pediatrics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1111\/ajt.15978","article-title":"Living-donor liver transplantation for liver hemorrhaging due to peliosis hepatis in X-linked myotubular myopathy: two cases and a literature review","volume":"20","author":"Shimizu","year":"2020","journal-title":"Am J Transplant"},{"key":"B24","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.legalmed.2019.04.005","article-title":"An autopsy case of peliosis hepatis with X-linked myotubular myopathy","volume":"38","author":"Funayama","year":"2019","journal-title":"Leg Med (Tokyo)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e621","DOI":"10.1002\/mgg3.621","article-title":"Three novel MTM1 pathogenic variants identified in Japanese patients with X-linked myotubular myopathy","volume":"7","author":"Nishikawa","year":"2019","journal-title":"Mol Genet Genomic Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.braindev.2017.12.014","article-title":"Successful use of non-invasive positive pressure ventilation in a patient with the severe form of X-linked myotubular myopathy","volume":"40","author":"Inoue","year":"2018","journal-title":"Brain Dev"},{"key":"B27","first-page":"34","article-title":"A case of X-linked myotubular myopathy with chylothorax","volume":"48","author":"Oishi","year":"2016","journal-title":"No to Hattatsu"},{"key":"B28","article-title":"X-Linked myotubular myopathy","volume-title":"GeneReviews[(R)]","author":"Dowling","year":"1993"},{"key":"B29","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3389\/fped.2019.00142","article-title":"Neonatal encephalopathy: need for recognition of multiple etiologies for optimal management","volume":"7","author":"Aslam","year":"2019","journal-title":"Front Pediatr"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.3390\/genes14112095","article-title":"Preimplantation genetic testing for genetic diseases: limits and review of current literature","volume":"14","author":"Giuliano","year":"2023","journal-title":"Genes (Basel)"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1735095\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:26:59Z","timestamp":1774848419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1735095\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":30,"alternative-id":["10.3389\/fped.2026.1735095"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1735095","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"article-number":"1735095"}}