Novel AMH and AMHR2 Mutations in Two Egyptian Families with Persistent Müllerian Duct Syndrome

Anti-müllerian hormone (AMH) is produced by Sertoli cells and signals through 2 transmembrane receptors (AMHR), specific types I and II, leading to regression of müllerian ducts during fetal male sex differentiation. Mutations in AMH and AMHR2 lead to the persistence of müllerian ducts in males which is transmitted in a recessive pattern. Here, we report 2 Egyptian DSD (disorder of sex development) patients reared as males who presented with bilateral cryptorchidism and otherwise normal male external genitalia and who both had a 46,XY karyotype. The first patient presented at the age of 2 years. Laparoscopic surgery revealed a uterus and fallopian tubes with the presence of 2 gonads, and biopsy and pathology revealed prepubertal testicular tissue showing small-sized tubules with mostly Sertoli cells and very few spermatogonia, edematous stroma, and no detectable ovarian tissue. The second patient presented at the age of 3 years. Laparoscopic surgery revealed a uterus and fallopian tubes, and serum AMH was very low (0.1 ng/mL). Molecular studies revealed a novel missense mutation in the AMHR2 gene in the first patient (c.767A>C; p.H256P) and a novel frameshift mutation in the AMH gene in the second patient (c.203delC; p.L70Cfs*7). We conclude that persistent müllerian ducts should be included in the differential diagnosis of cryptorchidism.