Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- Lynnette K Nieman, MD
Lynnette K Nieman, MD
- Section Editor — Adrenal Disease
- Senior Investigator
- Bethesda, MD
- Section Editors
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
- Benjamin A Raby, MD, MPH
Benjamin A Raby, MD, MPH
- Section Editor — Genetics
- Associate Professor of Medicine
- Harvard Medical School
Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol accounts for more than 90 percent of cases of congenital adrenal hyperplasia [1-3]. This conversion is mediated by 21-hydroxylase, or in current terminology, CYP21A2.
The most severely affected individuals with classic congenital adrenal hyperplasia due to CYP21A2 deficiency present during the neonatal period and early infancy with adrenal insufficiency with or without salt wasting, or later, with virilization. Females have genital ambiguity.
"Nonclassic," or late-onset CYP21A2 deficiency, does not manifest with neonatal genital ambiguity; rather, it presents later in life with signs of androgen excess. Clinical features in late childhood include premature pubarche, acne, and accelerated bone age; adolescent and adult females present with acne, hirsutism, and menstrual irregularity [4-10].
The pathophysiology, genetics, and clinical manifestations of the nonclassic form of congenital adrenal hyperplasia due to CYP21A2 deficiency are reviewed here. The diagnosis and treatment of late onset CP21A2 deficiency, and the classic form of CYP21A2 deficiency are reviewed separately. (See "Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children".)
Based upon neonatal screening studies that detect classic congenital adrenal hyperplasia, CYP21A2 deficiency is a common inherited disorder. The prevalence based upon such studies has been estimated to be about 1 in 14,200 live births, ranging from 1 in 28,000 in the Chinese to 1 in 280 in Yupik Eskimos. (See "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency", section on 'Prevalence'.)
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