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- What are the disorders associated with the simultaneous presence of both
Wolffi an and Mullerian duct derivates?
The causes of presence of both Wolffi an and Mullerian duct derivatives include
persistent Mullerian duct syndrome (PMDS), ovotesticular DSD (OT- DSD),
and mixed gonadal dysgenesis (MGD). Patients with PMDS usually present
with inguinal hernia but do not have genital ambiguity. PMDS occurs either due
to impaired secretion or action of AMH during early intrauterine life. Patients
with OT-DSD and MGD usually have genital ambiguity and have Wolffi an duct
derivatives on the side of testis/ovotestis and Mullerian duct derivatives on the
side of ovary/streak gonads.- Why boys with hypogonadotropic hypogonadism do not have genital
ambiguity?
The virilization of external genitalia during sexual differentiation is accom-
plished by the action of testosterone (after conversion to dihydrotestosterone)
secreted from the Leydig cells during 9–12 weeks of gestation. However, the
fetal hypothalamo–pituitary–testicular axis starts functioning only after
12 weeks of gestation. The prime drive for Leydig cell stimulation during this
critical period (9–12 weeks of gestation) is maternal human chorionic gonado-
tropin (hCG); hence, patients with isolated hypogonadotropic hypogonadism
(IHH) do not have genital ambiguity due to hCG-mediated testosterone
secretion from fetal Leydig cells. The activation of hypothalamo–pituitary–tes-
ticular axis after 12 weeks is required for the continued production of testoster-
one, which is responsible for penile growth and descent of testes. Hence,
patients with hypogonadotropic hypogonadism with decreased testosterone
levels manifests with micropenis and cryptorchidism. Rarely, patients with
DAX1 gene mutation may have genital ambiguity with IHH as DAX1 gene
mutation is also associated with impaired Leydig cell function.- Can patient with Klinefelter ’ s syndrome present with ambiguous genitalia?
Patients with Klinefelter’s syndrome do not have genital ambiguity as the pres-
ence of Y chromosome directs bipotential gonad to differentiate into testis and,
consequently, virilization of external genitalia. However, there are few reports
of genital ambiguity in patients with 47,XXY karyotype. This may be due to
higher number of CAG repeats in the androgen receptor (i.e., androgen insensi-
tivity) or double dose of DAX1 gene (as a result of failure of inactivation of
DAX1).9 Disorders of Sex Development