Association between genotype, clinical presentation, and severity of congenital adrenal hyperplasia: a review

Congenital adrenal hyperplasia (CAH) applies to a family of inherited disorders of steroidogenesis caused by an abnormality in one of the five enzymatic steps necessary in the conversion of cholesterol to cortisol. The enzyme defects are transmitted as an autosomal recessive trait. Patients with a "classical" form of CAH usually present during the neonatal and early infancy period with adrenal insufficiency, which could be associated with a salt- losing pathology. Females usually have genital ambiguity. Approximately 67% of classical CAH patients are classified as "salt-losing", while 33% have "non-salt-losing" or the "simple-virilizing" form, reflecting the degree of aldosterone deficiency. Non-classic 21-hydroxylase deficiency (NC 21-OHD) refers to the condition in which partial deficiencies of 21-hydroxylation produce less extreme hyperandrogenemia and milder symptoms. Females do not demonstrate genital ambiguity at birth. The gene for adrenal 21-hydroxylase, CYP21, is located on chromosome 6p in the area of human leukocyte antigen (HLA) genes. Specific mutations may be associated with a certain degree of enzymatic compromise and the clinical form of 21-hydroxylase deficiency (21-OHD). NC 21-OHD patients are predicted to have mild mutations on both alleles and one severe or one mild mutation of the 21-OH locus (compound heterozygote). This review aims to describe the association between the genotype and clinical presentations and severity of CAH.