Overview

Congenital adrenal hyperplasia (CAH) stemming from 11-beta-hydroxylase deficiency is part of a group of disorders collectively referred to as congenital adrenal hyperplasia. These conditions impact the adrenal glands, which are small structures situated above the kidneys that produce vital hormones essential for the body’s proper functioning. In individuals with CAH caused by 11-beta-hydroxylase deficiency, the adrenal glands generate excessive androgens, a category of hormones typically associated with male sexual traits.

This disorder occurs in two main forms: the classic and non-classic variations, with the classic form being the more severe of the two.

Females who have the classic variation of CAH due to 11-beta-hydroxylase deficiency often have external reproductive organs that appear ambiguous, neither distinctly male nor female. However, their internal reproductive organs develop as expected. Both males and females with the classic form experience early onset of secondary sexual characteristics, such as facial and pubic hair, voice deepening, acne, and an accelerated growth spurt. Interestingly, although this early growth spurt occurs, it may result in shorter adult height as growth can be stunted in later adolescent years. Moreover, about two-thirds of individuals with the classic form also present with elevated blood pressure (hypertension), typically arising during the first year of life.

In contrast, females with the non-classic form of CAH due to 11-beta-hydroxylase deficiency exhibit normal female genitalia. Over time, affected females may develop excessive facial or body hair (hirsutism) along with irregular periods. Males with the non-classic form generally exhibit no noticeable symptoms apart from reduced height, and hypertension is not a typical concern in this form of the disorder.

Prevalence

CAH due to 11-beta-hydroxylase deficiency represents 5 to 8 percent of all congenital adrenal hyperplasia cases. It is believed to affect between 1 in 100,000 to 200,000 newborns. Among Moroccan Jews living in Israel, this condition is more frequently seen, with instances at approximately 1 in every 5,000 to 7,000 infants. Additionally, the classic variation of CAH due to 11-beta-hydroxylase deficiency is reported to be significantly more prevalent than the non-classic form.

Underlying Causes

Mutations in the CYP11B1 gene are responsible for CAH due to 11-beta-hydroxylase deficiency. This gene provides the blueprint for an enzyme, 11-beta-hydroxylase, which operates in the adrenal glands to aid in the production of cortisol and corticosterone. Cortisol plays a pivotal role in maintaining blood sugar levels, managing stress, and reducing inflammation. Corticosterone, on the other hand, undergoes conversion into aldosterone, a hormone vital for blood pressure regulation by overseeing fluid and salt balance in the body.

This particular type of CAH results from a deficiency in the 11-beta-hydroxylase enzyme. When this enzyme is scarce, intermediate products destined to become cortisol or corticosterone instead accumulate and convert into androgens, leading to irregularities in sexual development, particularly noticeable in females. Excessive accumulations of corticosterone precursors also contribute to hypertension, primarily affecting individuals with the classic form.

The extent of enzyme functionality typically influences the severity of sexual development abnormalities. Generally, those who inherit the classic form have mutations in the CYP11B1 gene that result in either significantly reduced or entirely absent enzyme functionality. Conversely, individuals with non-classic CAH usually possess mutations that compromise but do not completely eliminate enzyme activity. Interestingly, the seriousness of sexual development symptoms does not always correlate with the severity of hypertension in affected people.

Further Insights on the Gene Involved with CAH Due to 11-Beta-Hydroxylase Deficiency

• CYP11B1

Genetic Inheritance

This disorder follows an autosomal recessive inheritance pattern. This means that both parents of an affected individual each carry one mutated copy of the gene, but do not typically exhibit any symptoms of the condition themselves.

Alternative Names for This Disorder

• 11 beta hydroxylase deficiency
• 11b hydroxylase deficiency
• Hypertensive form of adrenal hyperplasia
• Deficiency of steroid 11-beta-monooxygenase
• P450C11B1 deficiency
• Steroid 11 beta hydroxylase deficiency

Additional Resources & Information

Genetic Testing Resources

• Genetic Testing Registry: Deficiency of steroid 11-beta-monooxygenase

Genetic and Rare Diseases Information Center

• Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

Support and Advocacy Groups

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases by OMIM

• ADRENAL HYPERPLASIA, CONGENITAL, CAUSED BY STEROID 11-BETA-HYDROXYLASE DEFICIENCY

Scientific Research on PubMed

• PubMed

References

• Krone N, Riepe FG, Gotze D, Korsch E, Rister M, Commentz J, et al. Congenital adrenal hyperplasia due to 11-hydroxylase deficiency: functional characterization of two novel point mutations and a three-base pair deletion in the CYP11B1 gene. J Clin Endocrinol Metab. 2005 Jun;90(6):3724-30. doi: 10.1210/jc.2005-0089
• Nimkarn S, New MI. Steroid 11beta-hydroxylase deficiency congenital adrenal hyperplasia. Trends Endocrinol Metab. 2008 Apr;19(3):96-9. doi: 10.1016/j.tem.2008.01.002
• Parajes S, Loidi L, Reisch N, Dhir V, Rose IT, Hampel R, et al. Functional consequences of seven novel mutations in the CYP11B1 gene: four nonclassic and three classic mutations. J Clin Endocrinol Metab. 2010 Feb;95(2):779-88. doi: 10.1210/jc.2009-0651
• Peter M. Congenital adrenal hyperplasia: 11beta-hydroxylase deficiency. Semin Reprod Med. 2002 Aug;20(3):249-54. doi: 10.1055/s-2002-35389
• Zhu YS, Cordero JJ, Can S, Cai LQ, You X, Herrera C, et al. Mutations in CYP11B1 gene: phenotype-genotype correlations. Am J Med Genet A. 2003 Oct 15;122A(3):193-200. doi: 10.1002/ajmg.a.20108