A Novel MYRF Variant Presenting With Scimitar Syndrome, Hepatopulmonary Fusion, Right-Sided Congenital Diaphragmatic Hernia, and Uterine Didelphys.

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.