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Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Author
Deborah P Merke, MD, MS
Section Editors
Lynnette K Nieman, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol accounts for more than 90 percent of cases of congenital adrenal hyperplasia (CAH) [1-3]. This conversion is mediated by 21-hydroxylase, the enzyme encoded by the CYP21A2 gene.

Patients with “classic” or the most severe form of CAH due to 21-hydroxylase deficiency present during the neonatal period and early infancy with adrenal insufficiency with or without salt-losing, or as toddlers with virilization. Females have genital ambiguity.

“Nonclassic,” or late-onset 21-hydroxylase deficiency, presents later in life with signs of androgen excess, and without neonatal genital ambiguity. Clinical features in childhood may include premature pubarche, and accelerated bone age; adolescent and adult females may present with hirsutism, menstrual irregularity, infertility, and acne. Some patients with nonclassic CAH remain asymptomatic.

The pathophysiology, genetics, and clinical manifestations of CAH due to CYP21A2 mutations will be reviewed here. The diagnosis and treatment of classic 21-hydroxylase deficiency in adults and in children, and an overview of nonclassic and unusual CAHs are discussed elsewhere. (See "Diagnosis 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" and "Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Uncommon congenital adrenal hyperplasias".)

PREVALENCE

Based upon neonatal screening studies that detect classic congenital adrenal hyperplasia (CAH), 21-hydroxylase deficiency is one of the more common inherited disorders. Data from approximately 6.5 million newborn infants screened worldwide shows an estimate of approximately 1 in 15,000 livebirths [4,5]. Prevalence varies according to ethnicity and geographic area. This number varies from as low as 1 in 28,000 in the Chinese population [6], to 1 in 5000 to 23,000 live births in Caucasian [7,8], to as high as 1 in 280 in Yupik Eskimos in Alaska [9] and 1 in 2100 in the French island of La Reunion [5].

                 

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Literature review current through: Nov 2016. | This topic last updated: Wed Mar 18 00:00:00 GMT+00:00 2015.
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