Two Cases of MYRF-Related Differences of Sex Development: A Wide Phenotypic Spectrum

MYRF-related disorder is a recently described rare etiology of differences of sex development (DSD) caused by pathogenic variants in the MYRF gene on chromosome 11. MYRF encodes a membrane-bound transcription factor that is important in the early development of the eyes, lungs, diaphragm, heart, and genitourinary tract. With approximately 60 cases described, there is a need to better understand the associated phenotypes. We present 2 cases of 46, XY individuals found to have critical congenital cardiac disease prenatally, prompting genetic testing and, ultimately, variants in the MYRF gene to highlight the different phenotypes that can be seen in this disorder. Patient 1 had normal female genitalia, müllerian structures on imaging, and gonadal failure on biochemical testing. Conversely, patient 2 had perineal hypospadias, severe chordee, bifid scrotum, and bilateral cryptorchidism with normal testicular function in the mini-puberty period. Notably, both MYRF variants are novel and have not been previously reported in the medical literature, expanding the mutational and phenotypic spectrum of this condition.