{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:11:36Z","timestamp":1792458696836,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Craniofrontonasal dysplasia (CFND) is an X-linked developmental disorder caused by mutations in the EFNB1 gene located on chromosome Xq13. This gene encodes ephrin-B1, a ligand for Eph receptors, which is involved in cell signaling pathways and the development of the nervous and vascular systems, as well as facial and cranial structures. Paradoxically, the syndrome manifests with greater severity in heterozygous females, whereas hemizygous males typically present with mild or no abnormalities. Methods and Results: We report the case of a late preterm female neonate with dysmorphic features at birth, who subsequently developed necrotizing enterocolitis (NEC) caused by thrombosis of the superior mesenteric artery. Extensive bowel resection led to short bowel syndrome, resulting in cholestatic liver disease, malabsorption, and growth impairment. Array-comparative genomic hybridization (a-CGH) analysis identified a ~791 Kb microduplication at Xq13.1, encompassing the EFNB1 gene, confirming the diagnosis of CFND. She was enrolled in a multidisciplinary follow-up program and, at 2 years of age, presents with marked growth and neurodevelopmental delay. Conclusions: This report describes a rare association between CFND and NEC caused by superior mesenteric artery thrombosis. To the best of our knowledge, no previously reported cases of CFND associated with thrombosis or thrombosis-related conditions, including NEC, have been identified. This is based on a literature review (2004\u20132025) performed using PubMed and Scopus, and limited to English-language case reports and reviews.<\/jats:p>","DOI":"10.3390\/jcm14197055","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:05:06Z","timestamp":1759763106000},"page":"7055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Necrotizing Enterocolitis Due to Mesenteric Artery Thrombosis in a Patient with Craniofrontonasal Dysplasia: Casual or Causal Association?"],"prefix":"10.3390","volume":"14","author":[{"given":"Gregorio","family":"Serra","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Bacile","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-8035","authenticated-orcid":false,"given":"Maria Rita","family":"Di Pace","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Giliberti","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-1635","authenticated-orcid":false,"given":"Mario","family":"Giuffr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-1901","authenticated-orcid":false,"given":"Marco","family":"Pensabene","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Ranucci","sequence":"additional","affiliation":[{"name":"Pediatric Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), University of Pittsburgh Medical Center, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sergio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Corsello","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-6910","authenticated-orcid":false,"given":"Rosaria","family":"Nardello","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"ref_1","first-page":"85","article-title":"Craniofrontonasal dysplasia","volume":"15","author":"Cohen","year":"1979","journal-title":"Birth Defects Orig. Art. Ser."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.conb.2004.04.003","article-title":"Eph receptors in the adult brain","volume":"14","author":"Yamaguchi","year":"2004","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/s10038-019-0638-9","article-title":"Four novel mutations in EFNB1 in Indian patients with craniofrontonasal syndrome","volume":"64","author":"Howaldt","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_4","unstructured":"(2025, August 04). Valutazione Antropometrica Neonatale. Riferimento Carte INeS. Available online: http:\/\/www.inescharts.com."},{"key":"ref_5","unstructured":"(2025, August 04). DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans Using Ensembl Resources). Available online: https:\/\/www.deciphergenomics.org\/browser."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1148\/radiology.195.1.7892467","article-title":"Common bile duct in children: Sonographic dimensions","volume":"195","author":"Ambrosino","year":"1995","journal-title":"Radiology"},{"key":"ref_7","unstructured":"World Health Organization (2025, August 04). Child Growth Standards. Available online: https:\/\/www.who.int\/tools\/child-growth-standards\/standards."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2214\/ajr.157.1.2048509","article-title":"Normal splenic size in infants and children: Sonographic measurements","volume":"157","author":"Rosenberg","year":"1991","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/(SICI)1096-8628(19960111)61:2<147::AID-AJMG8>3.0.CO;2-U","article-title":"Craniofrontonasal syndrome: Study of 41 patients","volume":"61","author":"Saavedra","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1002\/ajmg.a.33596","article-title":"A novel EFNB1 mutation (c.712delG) in a family with craniofrontonasal syndrome and diaphragmatic hernia","volume":"152","author":"Hogue","year":"2010","journal-title":"Am. J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S1534-5807(03)00198-9","article-title":"Control of skeletal patterning by ephrinB1-EphB interactions","volume":"5","author":"Compagni","year":"2003","journal-title":"Dev. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1086\/421532","article-title":"Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome","volume":"74","author":"Wieland","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nature03479","article-title":"X-inactivation profile reveals extensive variability in X-linked gene expression in females","volume":"434","author":"Carrel","year":"2005","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15557","DOI":"10.1074\/jbc.M112.340869","article-title":"Possible role of Efnb1 protein, a ligand of Eph receptor tyrosine kinases, in modulating blood pressure","volume":"287","author":"Wu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13052-022-01403-6","article-title":"Intestinal malrotation in a female newborn affected by Osteopathia Striata with Cranial Sclerosis due to a de novo heterozygous nonsense mutation of the AMER1 gene","volume":"48","author":"Serra","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1534\/genetics.116.195917","article-title":"Insight into the RNA exosome complex through modeling pontocerebellar hypoplasia type 1b disease mutations in yeast","volume":"205","author":"Fasken","year":"2017","journal-title":"Genetics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa1516767","article-title":"Resolution of disease phenotypes resulting from multilocus genomic variation","volume":"376","author":"Posey","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rosina, E., Pezzani, L., Pezzoli, L., Marchetti, D., Bellini, M., Pilotta, A., Calabrese, O., Nicastro, E., Cirillo, F., and Cereda, A. (2022). Atypical, composite, or blended phenotypes: How different molecular mechanisms could associate in double-diagnosed patients. Genes, 13.","DOI":"10.3390\/genes13071275"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(01)00191-X","article-title":"The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration","volume":"104","author":"Adams","year":"2001","journal-title":"Cell"},{"key":"ref_20","unstructured":"(2025, September 28). Harmonizome. STARD8 Gene: GTPase-Activating Protein Regulating RhoA and Vascular Stability. Ma\u2019ayan Lab. Available online: https:\/\/maayanlab.cloud\/Harmonizome\/gene\/STARD8."},{"key":"ref_21","unstructured":"(2025, September 28). GeneCards. PJA1 Gene. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=PJA1."},{"key":"ref_22","first-page":"2","article-title":"Necrotizing enterocolitis in the preterm: Newborns medical and nutritional Management in a Single-Center Study","volume":"47","author":"Savarino","year":"2024","journal-title":"Ital. J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13052-022-01218-5","article-title":"Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sulfatase gene: Case report","volume":"48","author":"Schierz","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13052-023-01421-y","article-title":"New insights on partial trisomy 3q syndrome: De novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception","volume":"49","author":"Serra","year":"2023","journal-title":"Ital. J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e525","DOI":"10.1016\/j.ejmg.2011.06.011","article-title":"Xq12q13.1 microduplication encompassing the EFNB1 gene in a boy with congenital diaphragmatic hernia","volume":"54","author":"Petit","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.bbrc.2007.10.052","article-title":"START-GAP3\/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology","volume":"364","author":"Kawai","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1006\/geno.2002.6770","article-title":"PJA1, encoding a RING-H2 finger ubiquitin ligase, is a novel human X chromosome gene abundantly expressed in brain","volume":"79","author":"Yu","year":"2002","journal-title":"Genomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1055\/s-0036-1586102","article-title":"Portal Vein Thrombosis in a Preterm Newborn with Mutation of the MTHFR and PAI-1 Genes and Sepsis by Candida parapsilosis","volume":"33","author":"Serra","year":"2016","journal-title":"Am. J. Perinatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e7332","DOI":"10.1002\/ccr3.7332","article-title":"No, it is not mutually exclusive! A case report of a girl with two genetic diagnoses: Craniofrontonasal dysplasia and pontocerebellar hypoplasia type 1B","volume":"11","author":"Ibrahim","year":"2023","journal-title":"Clin. Case Rep."},{"key":"ref_30","first-page":"103294","article-title":"Severe craniofrontonasal syndrome in a male patient mosaic for a novel nonsense mutation in EFNB1","volume":"63","author":"Shotelersuka","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1002\/ajmg.a.61506","article-title":"Extracranial midline defects in a patient with craniofrontonasal syndrome with a novel EFNB1 mutation","volume":"182","author":"Zenteno","year":"2020","journal-title":"Am. J. Med. Genet. A"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/19\/7055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:29:57Z","timestamp":1759764597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/19\/7055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":31,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jcm14197055"],"URL":"https:\/\/doi.org\/10.3390\/jcm14197055","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]}}}