Only the 21-hydroxylase deficiency has been studied sufficiently, in part because it is not only the most frequent cause of genital ambiguity and congenital adrenal hyperplasia but also because of the high prevalence of the nonclassical, late onset forms of the disease. The genetic defect in virilizing adrenal hyperplasia is an autosomal recessive gene. Within families, the clinical picture is uniform, the type of syndrome (simple, salt-wasting, hypertensive) is usually but not always the same in affected siblings. The ratio in offspring of unaffected parents is one affected to three nonaffected individuals. Treated patients have a 1:100 to 1:200 chance of producing an affected infant. Males and females are at equal risk. On the basis of worldwide screening, the overall incidence of 21-hydroxylase deficiency is 1 per 14,000 births. The highest frequency for congenital adrenal hyperplasia is in Alaskan Yupik Eskimos.

The classic form is a relatively common inborn error of metabolism. One out of every 100 Caucasians is likely to be a genetic carrier of the classic type, and neonatal screening tests indicate an incidence of 1 in 14,000, which is equivalent to phenylketonuria.

For the nonclassic types, frequency rates established by the usual methodology (neonatal screening, case surveys) are likely to markedly underestimate what may be one of the most common autosomal recessive disorders in humans. Extrapolations from ACTH testing suggest the follittleing frequency.