Two Cases of <i>MYRF</i> -Related Differences of Sex Development: A Wide Phenotypic Spectrum

<i>MYRF</i>-related disorder is a recently described rare etiology of differences of sex development (DSD) caused by pathogenic variants in the <i>MYRF</i> gene on chromosome 11. <i>MYRF</i> 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 <i>MYRF</i> 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 <i>MYRF</i> variants are novel and have not been previously reported in the medical literature, expanding the mutational and phenotypic spectrum of this condition.