Second, hCG/LH receptor abnormalities within the testes can lead to Leydig cell aplasia/hypoplasia and impaired testosterone production. In contrast, disorders of MH and AMH receptors result in persistent miillerian duct syndrome (PMDS). Afected patients appear as males but have a persistent uterus and fallopian tubes due to failed AMH action.
Last, the androgen receptor may be defective and result in androgen-insensitivity syndrome (AIS). Resistance to androgens may be incomplete and associated with varying degrees of virilization and genital ambiguity. Milder forms have been described in men with severe male factor infertility and poor virilization.
Females with complete androgen-insensitivity syndrome (CAIS) appear as phenotypically normal females at birth. They often present at puberty with primary amenorrhea. External genitalia appear normal; scant or absent pubic and axillary hair are noted; the vagina is shortened or blind ending; and the uterus and fallopian tubes are absent. However, these individuals develop breasts during pubertal maturation due to abundant androgen to estrogen conversion. Testes may be palpable in the labia or inguinal area or may be found intraabdominally. Surgical excision of the testes after puberty is recommended to decrease the associated risk of germ cell tumors, which may be as high as 20 to 30 percent.
• 46,XX Disorders of Sex Development
As seen in Table 3-2, etiology of 46,X disorders of sexual differentiation may stem from abnormal ovarian development or from excess androgen exposure.
Disorders of ovarian development of those with a 46,X complement include: (1) gonadal dysgenesis, (2) testicular DSD, and (3) ovotesticular DSD.
With 4, X gonadal dysgenesis, similar to Turner syndrome, streak gonads develop. These lead to hypogonadism, prepubertal normal female genitalia, and normal miillerian structures, but other Turner stigmata are absent.
With 4,X testicuar DSD, several possible genetic mutations lead to testis-like formation within the ovary-streak gonad, dysgenetic testis, or ovotestis. Defects may stem from SRY translocation onto one X chromosome. In individuals without SRY translocation, other genes with testis-determining efects are most likely activated. Regardless, production of MH prompts miillerian system regression, and androgens promote wolian system development and external genitalia masculinization. Spermatogenesis, however, is absent due to a lack of needed genes on the long arm of the Y chromosome. hese individuals are not usually diagnosed until puberty or during infertility evaluation.
With 4,X ovotesticular DSD, individuals possess a unilateral ovotestis with a contralateral ovary or testis, or bilateral ovotestes. Phenotypic indings depend on the degree of androgen exposures and mirror those for other ovotesticular DSDs discussed on page 39.