Diagnosis of Ambiguous Genitalia in the Newborn

Diagnosis of Ambiguous Genitalia in the Newborn

When a genital defect is discovered in the neonatal period, complementary clinical, hormonal, genetic, molecular and radiographic investigations are needed to first diagnose the intersex state and then to determine the etiology and orient the therapeutic approach.

Clinical Investigations
Thorough physical examination is the key to diagnosis. Methodical general inspection will establish whether the genital defect is a sign of a malformation syndrome. Careful genital inspection will define the extent of the ambiguity by determining the presence, number, size, symmetry and position of gonads. In some cases, the sexual ambiguity is evident. For example, the genital tubercle may show development that is midway between that of a penis and a clitoris (the length and diameter, however, should be evaluated); the genital folds may be completely fused, with a bifid scrotum; the penis may appear abnormally bent and buried or sunken inward; or the urethral orifice may open toward the inner side of the penis, indicating hypospadias. Other signs include posterior fusion of the labia majora and a single perineal orifice at the base of the genital tubercle, between the genital folds, signaling the existence of a urogenital sinus.

Quite often, however, the genital malformation is less obvious. When the malformation is not easy to determine, the clinician's attention should be drawn to the following: an association of cryptorchidism and hypospadias, bilateral cryptorchidism, true clitoridal hypertrophy of the gland and not of the hood, and an oblong mass in the inguinal position in a newborn with female phenotype.

Precise measurement of the penis should be made. The mean stretched penile length in the normal full term newborn male is 3.5 cm (±0.5 cm).

Once the examination has been completed, the clinician should be ready to classify the degree of ambiguity of the external genitalia (genital tubercle and folds and the urogenital sinus). Prader's five stages may be used or, as is now more often the case, Quigley's 6–7 stages, which offer the advantage of greater descriptive detail.

Grade 1: Individuals with normal male external genitalia such as infertile males with azoospermia and hormonal features of androgen resistance, those with reduced virilization at puberty (so-called 'minimal' androgen resistance).

Grade 2: Individuals who have a univocally male phenotype, but who have mildly defective fetal masculinization, manifested by defects such as isolated hypospadias and/or micropenis.

Grade 3: Individuals with predominantly male phenotype but with more severely defective masculinization in utero, as evidenced by perineal hypospadias, small penis, and cryptorchidism and/or bifid scrotum.