MYRF gene mutation leading to coronary artery anomaly combined with 46,XY sex development disorder, a case report and literature review.

backgroundMYRF gene mutations can lead to the development of Cardio-Urogenital Syndrome (CUGS), characterized by congenital heart disease, abnormalities in the internal and external reproductive organs, and ocular anomalies. CUGS can manifest with various types of congenital heart diseases, such as Tetralogy of Fallot, Scimitar syndrome, Hypoplastic Left Heart Syndrome, Atrial Septal Defect, Ventricular Septal Defect, Dextrocardia, Aortic Arch Anomalies, and Pulmonary Vein Anomalies et al. Male patients (46,XY) may present with unilateral cryptorchidism, ambiguous genitalia, or even typical female genitalia. The most common ocular issues consistent with high myopia and nanophthalmos. To date, there have been reports of over 30 cases of MYRF gene mutations worldwide. CASE REPORT: A 5-month-old female infant was admitted to Beijing Children's Hospital affiliated with Capital Medical University due to "rapid breathing since birth." No targeted therapy was administered prior to admission despite persistent tachypnea. Four months before admission, the infant was seen at a local hospital due to abnormalities in the external reproductive organs. Chromosomal analysis revealed 46, XY, and whole exome gene testing showed a MYRF gene mutation, identified heterozygosity for de novo mutations in the MYRF gene, splice site variant, respectively, that was not found in the gnomAD database, clinically presenting as Cardio-Urogenital Syndrome (GUGS; OMIM: 618280), inherited in an autosomal dominant (AD) manner. Family history was negative. The infant's showed severely breathing progressively, leading to admission to our hospital. Electrocardiography showed pathological Q waves in leads I, avL, and V4-V6. Echocardiography revealed congenital heart disease of anomalous origin of the left coronary artery from the pulmonary artery, severe left ventricular enlargement (left ventricular end-diastolic diameter 35.2 mm), mild-to-moderate mitral regurgitation, and slightly reduced left ventricular systolic function (EF: 54%, which is just below the normal threshold 55%). Subsequent coronary angiography indicated the left coronary artery originating from the main pulmonary artery. The infant underwent further surgical treatment which confirmed the prior diagnosis and had a good postoperative recovery.

conclusionThis case represents an exceptionally rare instance of MYRF-CUGS combined with coronary artery anomaly. This case report enriches the clinical phenotype spectrum of CUGS caused by MYRF gene mutations and improves recognition among clinicians.