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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 may be used 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 ambiguous genitalia, ambiguous genitals, abnormal genitalia, abnormal penis, abnormal vagina (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 between what one clinician might call "a disorder of sexual differentiation" and what another might refer to as "perineal hypospadias." In patients with hypospadias, the following additional features should prompt further investigation: a family history of hypospadias.

Hypospadias, genital ambiguity, and sex reversal are component features.

History and Physical Examination and Investigations

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.

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 is increased (e.g., an infant with congenital adrenal hyperplasia). Asymmetry of the labioscrotal folds is seen more often in cases of mixed gonadal dysgenesis and true hermaphroditism than in partial androgen insensitivity or testosterone biosynthetic defects. On a more general inspection, the infant may be found.

Gonadal Dysgenesis

Incomplete differentiation of the bipotential gonad into either an ovary or a testis (partial gonadal dysgenesis) is one of the most frequently encountered causes of genital ambiguity. Dysgenic testes may secrete insufficient amounts of both testosterone and

True Hermaphroditism.

When the gonads in one individual are comprised of both ovarian and testicular elements, the condition is called true hermaphroditism. The most common gonad found is an ovotestis, and gonads with purely ovarian tissue are more likely to be found on the left side. In most cases, any testicular tissue found is dysgenetic, and the ovarian tissue is normal. Most patients with

Defects in Steroid Hormone Biosynthesis

21-Hydroxylase Deficiency.

If the patient has an XX karyotype and ambiguous genitalia, the most likely diagnosis is congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. This condition results in increased ACTH secretion, which, in turn, results in hyperpigmentation of the

17beta-Hydroxysteroid Dehydrogenase Deficiency.

This defect impairs the conversion of androstenedione to testosterone in the testis. Sixty cases have been reported from one inbred community in the Gaza Strip. Inheritance is autosomal recessive. Most XY cases have either ambiguous or