Genetic sex is determined by the paternally inherited X or Y chromosome. Once established sexual determination, the commitment of the primordial gonads to becoming testes or ovaries, will follow and lead to the final phase of sexual differentiation which is the subsequent development of the internal and external genitalia. Sexual differentiation under normal circumstances is under the control of a 35 kb region of the Y chromosome known as the SRY gene. A defect anywhere in this process can cause disorders of sexual differentiation and can be classified as one of the following:
46,XY disorders of gonadal determination
46,XX disorders of gonadal determination
46,XY disorders of androgen biosynthesis and action
Luteinizing hormone (LH) receptor defects
Disorders of antimüllerian hormone (AMH) or antimüllerian hormone receptor
Fetal exposure to compounds with estrogenic effects (xenoestrogens) such as herbicides, pesticides, polychlorinated biphenyls (PCBs), polystyrenes, as well as antiandrogens such as the polyaromatic hydrocarbons, linuron, vinclozolin. Androgen exposure includes inadvertent contact by the mother with testosterone creams used by a family member or the mother taking progestin-containing oral contraceptives.
Diagnostic Criteria and Clinical Characteristics
Diagnostic Criteria for Sexual Differentiation
Diagnostic criteria should include
All those being evaluated for a disorder of sexual differentiation will need a rapid and complete evaluation including
Serum hormone concentrations
Extensive pedigree searching for abnormalities of sex development in family members including infertility
Clinical and Genetic Features of Sexual Differentiation
Table 63–1Hormonal and Genetic Aspects of Disorders of Sexual Differentiation |Favorite Table|Download (.pdf) Table 63–1 Hormonal and Genetic Aspects of Disorders of Sexual Differentiation
|46, XY DSD ||Inheritance ||External Genitalia ||Internal Genitalia ||Presentation ||Hormone profile ||Risk of gonadal tumor ||Treatment ||Chromosome |
|Complete Gonadal Dysgenesis ||AR, X-linked, Y-linked ||Female ||Female ||Present with pubertal delay, no secondary sex characteristics, primary amenorrhea || |
↑FSH, LH no ↑ in T with hCG.
Compete GD: ↓↓ T, DHT, E2
|Present || |
Estrogen replacement beginning at puberty
|Mixed/Partial GD ||AR, X-linked, Y-linked ||variable ||variable ||Ambiguous genitalia, pubertal delay, amenorrhea (depends on the amount of functional testicular tissue) ||Mixed/Partial GD: ↓ T, DHT, E2, nml to ↓AMH ||Present ||Estrogen if reared as female, Testosterone if reared as a male. ||Multiple:Yp11.39p24.39q3312q13.1 |
|Testicular Regression Syndrome ||AR limited to Males ||variable ||M ||Lack of secondary male characteristics || |
↓↓ T, DHT, E2
No response to hCG
|None ||Testosterone if reared as a male ||unknown |
|5α-reductase type 2 deficiency ||AR ||Ambiguous or F ||M ||Virilization during puberty, |
Nml FSH, LH
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