Chicago Center for Jewish Genetics Disorders - Ashkenazi Disorders: Non-Classical Adrenal Hyperplasia

Ashkenazi Disorders: Mendelian

Gene: The gene responsible for non-classical adrenal hyperplasia (NCAH) is the 21-Hydroxylase gene (CYP21), which is located at 6p21.3. This gene encodes 21-hydroxylase made by the adrenal cortex and it is involved in cortisol synthesis.

Mutations and testing: 3 mutations result in enzyme activity 20-50% of normal, which is associated with the non-classical, later-onset, more mild form of the disorder. These mutations are Exon 1 (P30L), Exon 7 (V281L), and P453S and are more common in the Ashkenazi Jewish population. NCAH has also been found at an increased incidence in Hispanics, Yugoslavs, and Italians.

Traits: The disorder is caused by a defect in cortisol synthesis. Cortisol deficiency results in increased ACTH release, which leads to an overproduction of cortisol precursors, such as 17-hydroxy progesterone, and subsequent over-production of androgens. Excess androgen production can lead to a spectrum of effects from mild virilization to "classical" congenital adrenal hyperplasia (in which there are severe and life-threatening hormonal and electrolyte imbalances). Although, the mild form occurs at an increased incidence in Ashkenazi Jews, the classical form does NOT occur any more frequently than in the general population, where the disease incidence estimated to be 1 in 8,000 to 1 in 13,000 births.

In the mild form symptoms typically appear at puberty and include severe acne, excess facial and body hair, early development of pubertal hair, receding scalp hairline, advanced bone age resulting in reduced adult stature, and menstrual disturbances. The effects of this become apparent in girls at puberty. Boys do not show any effects because testosterone production overrides the effects of increased adrenal androgens. The concommittent decrease in cortisol synthesis due to the enzyme defect is not clinically significant. There is no salt-wasting or virilization in NCAH.

Testing: Testing is mainly done for the "classical" congenital adrenal hyperplasia and has a detection rate of 95% in the general population.

Treatment: Treatment may not be necessary for non-classical adrenal hyperplasia. If necessary, supplemental glucocorticoids are used to suppress ACTH release.

Non-Classical Adrenal Hyperplasia from Geneclinics.org
http://www.genetests.org/profiles/cah

Reviewed by Dr. Joel Charrow, Children's Memorial Hospital.
1/03

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This page last updated on January 10, 2003.