A Hemizygous <italic>MED12</italic> Variant in Three Brothers with Hypomasculinized Genitalia and Additional Clinical Features: A Case Report.

INTRODUCTION

MED12 is a causative gene for congenital malformation syndromes. The association between MED12 variants and 46,XY disorders/differences of sex development (DSD) remains unclear, although several variant-positive patients exhibited genital abnormalities.

CASE PRESENTATION: Three siblings manifested hypomasculinized genitalia, including hypospadias and cryptorchidism, with normal or mildly increased gonadotropin levels. Two patients showed normal spontaneous puberty. Whole exome sequencing identified a maternally derived hemizygous MED12 variant (c.3064A>G, p.Met1022Val). One patient lacked typical clinical features of MED12-associated malformation syndromes.

CONCLUSION

MED12 variants may cause 46,XY DSD with or without congenital malformation syndromes through testicular dysfunction and defective genital formation during fetal development.