Necrotizing Enterocolitis Due to Mesenteric Artery Thrombosis in a Patient with Craniofrontonasal Dysplasia: Casual or Causal Association?

TL;DR

A rare case of a genetic disorder linked to a severe intestinal condition caused by blood clotting is reported, suggesting a possible connection.

Contribution

This is the first reported case linking craniofrontonasal dysplasia with necrotizing enterocolitis due to mesenteric artery thrombosis.

Findings

A neonate with craniofrontonasal dysplasia developed necrotizing enterocolitis from superior mesenteric artery thrombosis.

Genomic analysis confirmed a microduplication at Xq13.1 encompassing the EFNB1 gene.

The patient exhibited growth and neurodevelopmental delays at age two.

Abstract

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 (2004–2025) performed using PubMed and Scopus, and limited to English-language case reports and reviews.

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