5-Alpha-Reductase Deficiency Clinical Presentation

Diagnosis of 5-alpha-reductase type 2 deficiency (5-ARD) is usually made in the newborn period when the infant presents with ambiguous genitalia.^[7] No risk factors or clinical markers in pregnancy are known. Genital ambiguity is occasionally diagnosed prenatally when an infant who is demonstrated by amniocentesis or chorionic villus sampling to have XY karyotype fails to have a demonstrable penis on ultrasonography.

If 5-alpha-reductase deficiency is considered in a newborn, a broad approach to ambiguous genitalia should be taken.^{[1, 6]} The utmost care should be taken not to assign a gender to the child before evaluation and consultation with an experienced, multidisciplinary team. The first words spoken to the parents are likely to be remembered and should focus on the overall health of the infant. A sensitive discussion about the uncertainty of the child's gender and explanation of the child's genital anatomy can be aided by online developmental Web sites, such as the ones available on the Sick Kids and DSD Guidelines sites. See Ambiguous Genitalia and Intersexuality for more in depth discussion

Initial evaluation should begin with a careful history.^[1] Assess prenatal and maternal past medical and family history. Specific questions should be asked regarding relatives with disorders of sexual development (DSDs), neonatal deaths, amenorrhea, or infertility and consanguinity. Parental consanguinity increases the child's risk for autosomal recessive disorders including 5-alpha reductase type 2 deficiency.

Workup of ambiguous genitalia must include careful physical examination to characterize the degree of virilization on the Prader scale (see the image below), presence of palpable gonadal tissue, and overall health of the child.^[6]

Neonatal presentation

Phenotypic findings in a newborn are limited to the genitalia.^{[7, 8]} The spectrum of findings ranges from minimal undervirilization presenting with normal male anatomy, except for isolated micropenis or hypospadias, to severe undervirilization presenting as normal female external genitalia with mild clitoral enlargement as the only physical finding.

Most commonly, the external genitalia exhibit labial appearance to the labioscrotal folds with some mild rugation or pigmentation present in some patients.

The phallus is indeterminate in size. Its length falls between 1 cm (ie, usual maximum for a clitoris) and 2 cm (ie, lower limit of normal for a penis).

The urethra may empty anywhere from the tip of the phallus to the perineum, with the latter observed more often.

The testes are usually in the inguinal canals bilaterally; however, in some individuals with 5-alpha-reductase type 2 deficiency, the testes can be found in the labioscrotal folds or retained in the abdomen.

A pseudovaginal blind-ending introitus is usually present with a normal hymen.

Because the uterus is absent, rectal examination results are negative for a cervical mass.

The rest of the examination findings are within normal limits.

Presentation of males at puberty

Clear signs of virilization predominate at this age. The escutcheon is male in distribution. The phallus exhibits definite enlargement. The shoulders are relatively broad and the hips are narrow.

Muscularity and body hair may increase. No breast development is generally present. A prominent Adam's apple may start to develop. Facial hair develops. The child's voice may begin to deepen.

The mucosa of the vaginal introitus remains atrophic in appearance (remaining red) rather than the thickened pink of estrogen-stimulated mucosa.

Presentation of females

Females homozygous for 5-alpha-reductase type 2 deficiency have very subtle manifestations, such as delayed menarche, minimal acne, and minimal body hair.^[9] Fertility is normal in females.

The cause of 5-alpha-reductase type 2 deficiency is the deficiency of the type 2 isozyme of 5-alpha-reductase.

As with most single enzyme disorders, 5-alpha-reductase type 2 deficiency is an autosomal recessive trait and sex limited because the clinical syndrome only affects genetic males, with very subtle phenotypic findings in homozygous females.^[10]