Congenital adrenal hyperplasia: phenotype and genotype.

Abstract Congenital adrenal hyperplasia (CAH) is a monogenic autosomal recessive condition manifested as a heterogeneous phenotype and caused by mutations in the CYP21 gene on chromosome 6p21.3. More than 50 mutations have been described, of which about 10 types account for >90% of affected alleles. Concordance between genotype and phenotype is sufficiently robust to be of significant value in the diagnosis and management of the adrenal disorder. Knowledge of the genotype is essential in planning a strategy for prenatal treatment and useful in resolving diagnostic dilemmas in newborn screening programs, identifying nonclassic CAH in hyperandrogenic women with elevated 17-hydroxyprogesterone levels, and studying the role of 21-hydroxylase deficiency in adrenal 'incidentalomas'. CYP21 genotyping is also valuable in defining the requirement for glucocorticoid and mineralocorticoid replacement from infancy to adulthood. More detailed gene sequencing of the noncoding as well as the coding regions, together with analysis of other genes involved in steroid hormone production and action, will potentially be a significant step toward the goal of tailoring treatment to each individual.