Aromatase excess syndrome

Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome.

The prevalence of aromatase excess syndrome is unknown; more than 20 cases have been described in the medical literature.

Rearrangements of genetic material involving the CYP19A1 gene cause aromatase excess syndrome. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth.

The condition can result from several types of genetic rearrangements involving the CYP19A1 gene. These rearrangements alter the activity of the gene and lead to an increase in aromatase production. In affected males, the increased aromatase and subsequent conversion of androgens to estrogen are responsible for the gynecomastia and limited bone growth characteristic of aromatase excess syndrome. Increased estrogen in females can cause symptoms such as irregular menstrual periods and short stature.

Genetic Testing Information

• Genetic Testing Registry: Aromatase excess syndrome

Genetic and Rare Diseases Information Center

• Aromatase excess syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• AROMATASE EXCESS SYNDROME; AEXS

Scientific Articles on PubMed

• PubMed

• Fukami M, Shozu M, Ogata T. Molecular bases and phenotypic determinants of aromatase excess syndrome. Int J Endocrinol. 2012;2012:584807. doi: 10.1155/2012/584807. Epub 2012 Jan 26. Citation on PubMed or Free article on PubMed Central
• Fukami M, Shozu M, Soneda S, Kato F, Inagaki A, Takagi H, Hanaki K, Kanzaki S, Ohyama K, Sano T, Nishigaki T, Yokoya S, Binder G, Horikawa R, Ogata T. Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants. J Clin Endocrinol Metab. 2011 Jun;96(6):E1035-43. doi: 10.1210/jc.2011-0145. Epub 2011 Apr 6. Citation on PubMed
• Fukami M, Tsuchiya T, Vollbach H, Brown KA, Abe S, Ohtsu S, Wabitsch M, Burger H, Simpson ER, Umezawa A, Shihara D, Nakabayashi K, Bulun SE, Shozu M, Ogata T. Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression. J Clin Endocrinol Metab. 2013 Dec;98(12):E2013-21. doi: 10.1210/jc.2013-2520. Epub 2013 Sep 24. Citation on PubMed
• Shihara D, Miyado M, Nakabayashi K, Shozu M, Ogata T, Nagasaki K, Fukami M. Aromatase excess syndrome in a family with upstream deletion of CYP19A1. Clin Endocrinol (Oxf). 2014 Aug;81(2):314-6. doi: 10.1111/cen.12329. Epub 2013 Oct 18. No abstract available. Citation on PubMed