Rare Disorder of Sexual Differentiation Treated at Medanta

Persistent Mullerian Duct Syndrome (PMDS) is a disorder of sexual differentiation, in which males in addition to having normal male reproductive organs have mullerian duct derivatives including uterus, fallopian tubes, cervix and upper two thirds of vagina. It is a rare congenital disorder caused by either a mutation in the gene for Mullerian Inhibiting Substance (MIS) also referred to as Anti-Mullerian Hormone (AMH), or a defect in the receptor for MIS/AMH.

The testes and female reproductive organs are located in unusual positions. Occasionally, both testes are undescended (bilateral cryptorchidism) and the uterus is in the pelvis. More often, only  one testis descends into the scrotum .The descended testis pulls the fallopian tube and uterus into the track through which it has descended. This creates a condition called hernia uteri inguinalis, a form of inguinal hernia.

The condition was first described by Nilson in 1939, and since then over 200 cases have been reported in the English literature. The diagnosis is often incidental, during surgery for cryptorchidism, inguinal hernia or laparotomy for an unrelated cause, or during investigation for infertility in adulthood. Of almost all the cases of PMDS reported so far, very few have been diagnosed early in infancy. Awareness and early detection of PMDS helps in performing definitive surgery at an early age, thereby reducing the impact of various medical, social and psychological problems associated with this condition.

Case Study
A two-month-old infant reared as a male, presented on July 13, 2013 with a history of painful left inguino-scrotal swelling. On physical examination, there was a left irreducible inguinal hernia with right non-palpable undescended testis. On left inguinal exploration, ipsilateral gonad connected to fallopian tube and uterus were identified. On slight traction, the contralateral fallopian tube and gonad were delivered (Fig. 1). Wedge biopsies were taken from both the gonads. The processus vaginalis was sutured after repositioning all the above structures into the abdominal cavity. The post-operative course was uneventful.

Fig. 1 Midline rudimentary uterus (Ut) with fallopian tubes (FT). Both gonads (G) at the two ends. UB – Urinary bladder; (Inset) Lateral view.
UB – Urinary bladder, Ut – Uterus, V – Vagina, G – Gonad.

Gonadal biopsies showed immature seminiferous tubule. The karyotype was 46, XY. The levels of male and female hormones [testosterone, leutenizing hormone (LH), follicle stimulating hormone (FSH), 17-alpha hydroxy progesterone (AHP)] were within the normal limits for age. Baseline testosterone was 67 ng/dL and post HCG stimulation testosterone was 647 ng/dL, indicating a normally functioning testicular tissue. The AMH was <0.05 pmol/L, indicating type I defect.

Two months later, during the definitive surgery, the uterus, fallopian tubes and a portion of vagina as distal as possible were excised with mucosal stripping of the remnant vagina (Fig. 2a). Owing to close anatomic association, a sliver of uterine walls was left attached to the vas bilaterally in order to preserve their blood supply. Intrascrotal positioning of testes (Fig. 2b) and biopsy confirmation of infantile uterus with bilateral tubal structures was done.

Fig. 2 a. Partial dissection of vas deference (Vd) from lateral wall of vagina done on the right side. b. Bilateral gonads fully mobilized for orchidopexy; (Inset) Specimen showing rudimentary uterus (Ut) with partially resected vagina (V) with fallopian tubes (FT).

The genetic study on this baby revealed a variant of AMH which is autosomal recessive, likely pathogenic. The parents were advised to get their genetic study as well.

Fig. 3 External genitalia with bilateral descended testes.
Six years post-surgery.

In conclusion, the baby presented with an irreducible left inguinal hernia with right impalpable testis. The operative findings of a uterus with bilateral fallopian tubes clinched the diagnosis of Persistent Mullerian Duct Syndrome. The baby has been on regular yearly follow up. Fig. 3 is a six-year post-op image showing  both testes in the scrotum and a normal penis. This boy will be sexually active as both testes are viable and producing hormones but the spermatogenesis is impaired and fertility in PMDS is anecdotal.