Genetic variants in the CYP21A2 gene cause a disturbance in the development of the enzyme, leading to congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Gene conversion events involving the functional gene and the pseudogene account for many cases of steroid 21-hydroxylase deficiency. CAH is an autosomal recessive disorder. There are multiple forms of CAH, defined as classical and nonclassical forms based on the amount of enzyme function still present in the patient.
The classical forms occur in approximately 1 in  to 1 in  births globally, and includes both the salt-wasting (excessive excretion of sodium via the urine causing hyponatremia and dehydration) and simple-virilizing forms. Complete loss of enzymatic activity causes the salt-wasting form. Variations in the structure of steroid 21-hydroxylase are related to the clinical severity of congenital adrenal hyperplasia. Cortisol and aldosterone deficits are associated with life-threatening sodium loss, as the steroids play roles in regulating sodium homeostasis. Simple-virilizing CAH patients (~1-2% enzyme function) maintain adequate sodium homeostasis, but exhibit other symptoms shared by the salt-wasting form, including accelerated growth in childhood and ambiguous genitalia in female neonates.
The nonclassical form is the mildest condition, retaining about 20% to 50% of enzyme function. This form is associated with mild and clinically silent cortisol impairment, but an excess of androgens post-puberty.