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The XX Male

In this rare condition, the phenotype resembles Klinefelter's syndrome (XXY) in that the testes are small (pealike) and dysgenetic, such that infertility is inevitable. Patients can be normal males or somewhat eunuchoid with gynecomastia in the XX male. Mullerian structures are absent. The hypothesis that testes develop because of a small Y-to-X translocation bearing the testis-determining gene is borne out.

XX male Y chromosome-derived DNA is apparently absent in the remaining 10% (although DNA of gonadal origin has not always been studied). It remains possible that, in some cases, testis determination can occur in the absence of SRY, and the existence of downstream non-Y testis-determining genes has been postulated. A variant of XX male syndrome has been reported in three cases in which the genitalia were ambiguous, both wolffian and mullerian structures were present, and yet the gonads were not ovotestes.

Phenotype 3: The Infant with Ambiguous Genitalia

If an infant has a phallus that is intermediate in size between a normal penis and a normal clitoris, an aberrantly located urethral opening, and at least one impalpable gonad, the term ambiguous genitalia.

The two most likely diagnoses are congenital adrenal hyperplasia (21-hydroxylase deficiency) and gonadal dysgenesis (including true hermaphroditism). Partial androgen insensitivity syndrome (PAIS) and 17beta-hydroxysteroid dehydrogenase deficiency (a defect in testosterone biosynthesis) are next in order of prevalence, followed by a group of very rare conditions (11beta-hydroxylase deficiency, 3beta-hydroxysteroid dehydrogenase deficiency, 5alpha-reductase deficiency, 17alpha-hydroxylase deficiency, placental aromatase deficiency, and LH receptor mutations). In at least one third of cases, even the most thorough investigation fails to reveal the underlying cause. There is no clear distinction.

Questions that should be asked on history taking are as follows: Was the mother taking any medications during pregnancy that could affect fetal genital development? Does she have any symptoms or signs of a virilizing disorder? Is there a family history of ambiguous genitalia or of perinatal death? Because genital appearances in such cases are highly variable, a staging system is extremely useful . According to the Prader classification, external genital appearances are given one of six grades from O (female) to V (male) according to the relative size of the phallus, the number of orifices, and the degree of midline fusion. Having defined the Prader grade by inspection of the genitalia, the examiner looks for other clues to the diagnosis. Careful inspection under daylight or a white light source may reveal a brownish-yellow hyperpigmentation of the genital skin if ACTH secretion.