303- What are the causes of 46 , XY DSD with ambiguous genitalia?
The causes of ambiguous genitalia in a 46,XY individual are enlisted in the
table given below.Pathogenesis Etiology
Disorders of testicular development Partial gonadal dysgenesis
Ovotesticular DSD
Disorders of androgen biosynthesis CAH
StAR inactivating mutation
CYP11A1 defi ciency
3 β-HSD2 defi ciency
P450 oxidoreductase defi ciency
17 β-HSD3 defi ciency
5 α-reductase defi ciency
LH receptor inactivating mutation
Disorders of androgen action Partial androgen insensitivity- What are the causes of 46 , XY DSD with female external genitalia?
The disorders commonly associated with female external genitalia in a 46,XY
individual include complete gonadal dysgenesis, complete androgen insensi-
tivity syndrome (CAIS), and androgen biosynthetic defect due to
17 α-hydroxylase and 17β-hydroxysteroid dehydrogenase type 3 defi ciency.
All these disorders present during adolescence with primary amenorrhea. Tall
stature, absent secondary sexual characteristics, and presence of Mullerian
derivatives suggest a diagnosis of 46,XY complete gonadal dysgenesis
(Swyer syndrome). Patients with CAIS are characterized by normal breast
development, absent pubic and axillary hair, and lack of Mullerian deriva-
tives. Presence of hypertension, absent secondary sexual characteristics, and
lack of Mullerian derivatives suggest a diagnosis of 17 α-hydroxylase defi -
ciency. Patients with 17β-hydroxysteroid dehydrogenase type 3 defi ciency
have female external genitalia at birth; however, they virilize during peripu-
bertal period. In addition, other disorders associated with defective androgen
biosynthesis like inactivating mutation of LH receptor, StAR protein, and
side chain cleavage enzyme (CYP11A1) can also result in female external
genitalia in a 46,XY individual (Fig. 9.6 ).9 Disorders of Sex Development