{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:07:22Z","timestamp":1784297242481,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL140024"],"award-info":[{"award-number":["HL140024"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cant\u00fa syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in <jats:italic>ABCC9<\/jats:italic> and <jats:italic>KCNJ8<\/jats:italic> genes. These genes encode gain\u2010of\u2010function mutations in the regulatory (SUR2) and pore\u2010forming (Kir6.1) subunits of K<jats:sub>ATP<\/jats:sub> channels, respectively, suggesting that channel\u2010blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous <jats:italic>ABCC9<\/jats:italic> variant (c.3347G&gt;A, p.Arg1116His), born prematurely at 32\u2009weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05\u2009mg<jats:sup>\u20131<\/jats:sup> kg<jats:sup>\u20131<\/jats:sup> day<jats:sup>\u20131<\/jats:sup> in two divided doses). After 1\u2009week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15\u2009mg<jats:sup>\u22121<\/jats:sup> kg<jats:sup>\u22121<\/jats:sup>day<jats:sup>\u22121<\/jats:sup> over the next 12\u2009weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS.<\/jats:p>","DOI":"10.1002\/ajmg.a.61200","type":"journal-article","created":{"date-parts":[[2019,6,8]],"date-time":"2019-06-08T04:49:00Z","timestamp":1559969340000},"page":"1585-1590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Glibenclamide treatment in a Cant\u00fa syndrome patient with a pathogenic <i>ABCC9<\/i> gain\u2010of\u2010function variant: Initial experience"],"prefix":"10.1002","volume":"179","author":[{"given":"Alan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Children's Hospital at Westmead, Sydney Children's Hospital Network  Sydney New South Wales Australia"},{"name":"Discipline of Genomic Medicine Sydney Medical School, University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Gurnasinghani","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Children's Hospital at Westmead, Sydney Children's Hospital Network  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin P.","family":"Kirk","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics Sydney Children's Hospital, Sydney Children's Hospital Network  Sydney New South Wales Australia"},{"name":"NSW Health Pathology East Genomics Laboratory  Sydney New South Wales Australia"},{"name":"School of Women's and Children's Health, University of NSW  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"McClenaghan","sequence":"additional","affiliation":[{"name":"Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine  St. Louis Missouri"},{"name":"Department of Cell Biology and Physiology Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy K.","family":"Grange","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Pandit","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Sleep Medicine The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung","family":"Zhu","sequence":"additional","affiliation":[{"name":"NSW Health Pathology East Genomics Laboratory  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Roscioli","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics Sydney Children's Hospital, Sydney Children's Hospital Network  Sydney New South Wales Australia"},{"name":"NSW Health Pathology East Genomics Laboratory  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Elakis","sequence":"additional","affiliation":[{"name":"NSW Health Pathology East Genomics Laboratory  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buckley","sequence":"additional","affiliation":[{"name":"NSW Health Pathology East Genomics Laboratory  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavesh","family":"Mehta","sequence":"additional","affiliation":[{"name":"Grace Centre for Newborn Intensive Care The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Mervis","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-9359","authenticated-orcid":false,"given":"Andrew","family":"Biggin","sequence":"additional","affiliation":[{"name":"Children's Hospital Westmead Clinical School, University of Sydney  New South Wales Australia"},{"name":"Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-2134","authenticated-orcid":false,"given":"Colin G.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine  St. Louis Missouri"},{"name":"Department of Cell Biology and Physiology Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25495"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051247"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30106-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2013.09.009"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00281261"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22555"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr019"},{"key":"e_1_2_6_9_1","volume-title":"GeneReviews\u00ae","author":"Grange D. 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