Gul Sher, Samantha Weaver, Rahul Adwani, Jai Parkash Udassi
West Virginia University Golisano Children’s Hospital and West Virginia University School of Medicine
United States
Case Reports in Pediatrics
Case Rep Pediatr 2026;
DOI: 10.1155/crpe/8646210
Abstract
The MYRF gene encodes a pleiotropic transcription factor essential for the development of multiple organ systems, including the heart, lungs, diaphragm, and genitourinary tract. Pathogenic variants in MYRF are associated with a multisystem disorder commonly referred to as MYRF-related cardiac-urogenital syndrome (CUGS). We describe a term female neonate with a maternally inherited likely pathogenic MYRF variant (c.1305_1311 + 1dup), a splice-site duplication predicted to disrupt normal gene function. The patient presented with complex congenital anomalies, including scimitar syndrome, right-sided congenital diaphragmatic hernia with hepatopulmonary fusion, pulmonary hypoplasia, and uterine didelphys. Several of these features have been individually reported in association with MYRF; however, uterine didelphys represents a previously unreported Müllerian duct anomaly within the MYRF-related phenotypic spectrum. The clinical course was complicated by severe pulmonary hypertension, refractory hypoxemia, and necrotizing enterocolitis, culminating in neonatal death despite aggressive medical management. This case highlights a severe neonatal presentation of MYRF-related disease in a female patient with an inherited pathogenic variant and expands the recognized phenotypic spectrum to include uterine didelphys. Recognition of sex-specific manifestations and variable penetrance in MYRF-related disorders is important for accurate diagnosis, prognostication, and genetic counseling in neonates with multisystem congenital anomalies.
Category
Class III. Pulmonary Hypertension Associated with Lung Hypoplasia
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes