305- What are the causes of 46 , XX DSD with ambiguous genitalia?
The causes of ambiguous genitalia in a 46,XX individual are enlisted in the
table given below.Pathogenesis Etiology
Disorders of gonadal
developmentOvotesticular DSD
Testicular DSD
SRY gene translocation
SOX9 duplication
Inactivating mutation of RSPO1 and WNT4
Disorders of androgen excess Congenital adrenal hyperplasia
2 1α-hydroxylase defi ciency
1 1β-hydroxylase defi ciency
P450 oxidoreductase defi ciency
3 β-HSD2 defi ciency
Placental aromatase defi ciency
Luteoma of pregnancy
Exogenous androgens exposure during intrauterine period- What are the causes of 46 , XX DSD with apparently male external genitalia?
The prerequisite for having apparently male external genitalia (Prader stage 5)
in a 46,XX individual is exposure to androgens during the critical period of
embryogenesis, i.e., between 8 and 12 weeks of gestation. Exposure to andro-
gens after this period results only in isolated clitoromegaly. The causes of
46,XX DSD with male external genitalia (but with anorchidism) include CAH
due to 21α-hydroxylase and 11β-hydroxylase defi ciency, SRY gene transloca-
tion, SOX9 duplications, and RSPO1 inactivating mutations. In addition,
maternal exposure to androgens/androgenic progestins during fi rst trimester
may also result in 46,XX DSD with male external genitalia.9 Disorders of Sex Development