Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as "bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition.

As Werner syndrome progresses, affected individuals may develop disorders of aging early in life, such as cloudy lenses (cataracts) in both eyes, skin ulcers, type 2 diabetes, diminished fertility, severe hardening of the arteries (atherosclerosis), thinning of the bones (osteoporosis), and some types of cancer. It is not uncommon for affected individuals to develop multiple, rare cancers during their lifetime. People with Werner syndrome usually live into their late forties or early fifties. The most common causes of death are cancer and atherosclerosis.

Werner syndrome is estimated to affect 1 in 200,000 individuals in the United States. This syndrome occurs more often in Japan, affecting 1 in 20,000 to 1 in 40,000 people.

Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA. This protein also assists in the process of copying (replicating) DNA in preparation for cell division. Mutations in the WRN gene often lead to the production of an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported to the cell's nucleus, where it normally interacts with DNA. Evidence also suggests that the altered protein is broken down more quickly in the cell than the normal Werner protein. Researchers do not fully understand how WRN mutations cause the signs and symptoms of Werner syndrome. Cells with an altered Werner protein may divide more slowly or stop dividing earlier than normal, causing growth problems. Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause the health problems associated with this condition.

Genetic Testing Information

• Genetic Testing Registry: Werner syndrome

Genetic and Rare Diseases Information Center

• Werner syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• WERNER SYNDROME; WRN

Scientific Articles on PubMed

• PubMed

• Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67. doi: 10.1002/humu.20337. Citation on PubMed or Free article on PubMed Central
• Kudlow BA, Kennedy BK, Monnat RJ Jr. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol. 2007 May;8(5):394-404. doi: 10.1038/nrm2161. Citation on PubMed
• Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr. Spectrum and risk of neoplasia in Werner syndrome: a systematic review. PLoS One. 2013;8(4):e59709. doi: 10.1371/journal.pone.0059709. Epub 2013 Apr 1. Citation on PubMed
• Lee JW, Harrigan J, Opresko PL, Bohr VA. Pathways and functions of the Werner syndrome protein. Mech Ageing Dev. 2005 Jan;126(1):79-86. doi: 10.1016/j.mad.2004.09.011. Citation on PubMed
• Maierhofer A, Flunkert J, Oshima J, Martin GM, Poot M, Nanda I, Dittrich M, Muller T, Haaf T. Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes. Aging Cell. 2019 Oct;18(5):e12995. doi: 10.1111/acel.12995. Epub 2019 Jul 1. Citation on PubMed
• Opresko PL, Calvo JP, von Kobbe C. Role for the Werner syndrome protein in the promotion of tumor cell growth. Mech Ageing Dev. 2007 Jul-Aug;128(7-8):423-36. doi: 10.1016/j.mad.2007.05.009. Epub 2007 May 31. Citation on PubMed
• Oshima J, Martin GM, Hisama FM. Werner Syndrome. 2002 Dec 2 [updated 2021 May 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1514/ Citation on PubMed
• Oshima J, Sidorova JM, Monnat RJ Jr. Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev. 2017 Jan;33:105-114. doi: 10.1016/j.arr.2016.03.002. Epub 2016 Mar 15. Citation on PubMed
• Shamanna RA, Croteau DL, Lee JH, Bohr VA. Recent Advances in Understanding Werner Syndrome. F1000Res. 2017 Sep 28;6:1779. doi: 10.12688/f1000research.12110.1. eCollection 2017. Citation on PubMed
• Takemoto M, Mori S, Kuzuya M, Yoshimoto S, Shimamoto A, Igarashi M, Tanaka Y, Miki T, Yokote K. Diagnostic criteria for Werner syndrome based on Japanese nationwide epidemiological survey. Geriatr Gerontol Int. 2013 Apr;13(2):475-81. doi: 10.1111/j.1447-0594.2012.00913.x. Epub 2012 Jul 23. Erratum In: Geriatr Gerontol Int. 2022 Jul;22(7):543. doi: 10.1111/ggi.14436. Citation on PubMed
• Yokote K, Chanprasert S, Lee L, Eirich K, Takemoto M, Watanabe A, Koizumi N, Lessel D, Mori T, Hisama FM, Ladd PD, Angle B, Baris H, Cefle K, Palanduz S, Ozturk S, Chateau A, Deguchi K, Easwar TK, Federico A, Fox A, Grebe TA, Hay B, Nampoothiri S, Seiter K, Streeten E, Pina-Aguilar RE, Poke G, Poot M, Posmyk R, Martin GM, Kubisch C, Schindler D, Oshima J. WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects. Hum Mutat. 2017 Jan;38(1):7-15. doi: 10.1002/humu.23128. Epub 2016 Oct 7. Citation on PubMed