Question

In an XX fetus with severe CAH, external genitalia will usually be male. Describe two possible situations where an XX fetus with severe CAH could instead develop female external genitalia. For each situation, explain how it would lead to the development of female external genitalia in the presence of high levels of testosterone.

Answer 1

Congenital adrenal hyperplasia is an inherited condition caused by mutations in genes that code for enzymes involved in making steroid hormones in the adrenal glands. The most common enzyme defect, 21-hydroxylase deficiency, leads to excess amounts of male hormones being produced by the adrenal glands.

The condition is inherited and passed on by an autosomal recessive gene. Autosomal recessive means that each parent carries one copy of the gene and passes on the gene to the child. Carrier parents have a 1 in 4 chance of having a child with this condition with each pregnancy. Girl babies with the condition have atypical genitalia. Boy babies don't.

In some cases, the mother of a child with this condition can be given medicines during pregnancy to lessen the effects of the enzyme deficiency if the baby is female.

Another type of CAH is called salt-losing. This is very serious and often fatal. It causes an electrolyte collapse in the newborn. Treatment is available if diagnosed early. Boys and girls are equally affected.

Many genetic and environmental factors can affect the developing baby and lead to atypical genitalia. Ambiguous genitalia may make it harder to determine a baby’s gender. But very few newborns with this condition have genitals that are so ambiguous that the healthcare provider can’t figure out the gender at birth.

These are far more common at birth:

• A girl baby with too much of the male hormones (virilization) who seems to have a small peni.s.

• A boy baby with an abnormally small penis.s that looks like a female clitoris. This is either because the baby did not respond to male hormones or the baby did not make male hormones.

In its absence, whether ovaries are present or not, the vagin.a develops and the labioscrotal swellings do not fuse. Testosterone is the hormone responsible for the male differentiation of the urogenital sinus and the external genitalia.

Females develop internal genitalia from unopposed müllerian structures as delineated above, and external genitalia develop when they are not exposed to androgens.