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Werner Syndrome Clinical Presentation

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Jun 13, 2016


In young adults, mutation in the WS gene is believed to be associated with clinical symptoms typically found in elderly individuals.

The most important feature of WS is healthy development in the patient's first decade of life.

Adult progeria is usually diagnosed on the basis of characteristic clinical features and typical concomitant diseases.

The hallmark of this syndrome is a striking disproportion between the patient's real age and the patient's appearance.

In general, this is an adult-onset disorder, with the earliest sign the lack of a growth spurt during adolescence.[5] A prematurely aged appearance with gray hair and sclerodermatous cutaneous changes begins in the 20-30s in association with cataracts, diabetes mellitus, atherosclerosis, cancers, and osteoporosis.

Metabolic abnormalities, including insulin resistance, may not be a pivotal part at disease onset.[16]



Perform a thorough clinical and laboratory examination, keeping in mind the patient's increased risk of neoplasms.

Characteristic clinical features of the disease

General appearance is as follows:

  • Short stature, usually less than 1.60 m, is observed.
  • Thin skin is present on the acral surfaces.
  • Muscle atrophy is noted.
  • The skull is relatively large, with a disproportionate lower part of the face.

Skin findings are as follows:

  • Wrinkling and aging of the face occurs.
  • A sclerodermalike appearance with nose and lip atrophy is typical.
  • The nose is pinched, and the cheeks are sunken because of fat loss, which causes the birdlike facial appearance.
  • Loss of subcutaneous fat complicated with ulceration can be observed on the shins and feet.
  • In most patients, calluses, hyperkeratosis, and ulcerations on the soles are present mainly over bony prominences.

Graying of the hair, loss of hair, and nail dystrophy usually are observed.

A high-pitched voice is characteristic.

Related diseases

Cataracts, as follows:

  • Rapidly progressing cataracts typically occur when patients are aged 20-40 years.
  • Cataracts are usually posterior and subcapsular.
  • Osteoporosis: Disturbances in the parathyroid glands are the main cause of osteoporosis.
  • Diabetes mellitus

Neoplasia, as follows:

  • Hematologic malignancies (leukemia and preleukemic conditions of the bone marrow [17] )
  • Carcinomas of the thyroid [17] and other organs
  • Sarcomas (soft tissue [17] ) [18]
  • Meningiomas [17]
  • Cutaneous malignancies, including malignant melanoma [17]
  • Possible evolution of ankle and heel ulcers into squamous cell carcinomas
  • Hyperthyreosis
  • Pituitary dysfunction
  • Vascular changes (arteriosclerotic type)
  • Hypogonadism or agonadism and premature menopause
  • Soft tissue calcification
  • Primary bone neoplasms [17]


WS is a genetic disorder. See Pathophysiology.

Contributor Information and Disclosures

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


Anna Wozniacka, MD, PhD Professor, Department of Dermatology, Medical University of Lodz, Poland

Anna Wozniacka, MD, PhD is a member of the following medical societies: European Academy of Dermatology and Venereology, Polish Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Franklin Flowers, MD Department of Dermatology, Professor Emeritus Affiliate Associate Professor of Pathology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery

Disclosure: Nothing to disclose.

  1. Nehlin JO, Skovgaard GL, Bohr VA. The Werner syndrome. A model for the study of human aging. Ann N Y Acad Sci. 2000 Jun. 908:167-79. [Medline].

  2. Davis T, Wyllie FS, Rokicki MJ, Bagley MC, Kipling D. The role of cellular senescence in Werner syndrome: toward therapeutic intervention in human premature aging. Ann N Y Acad Sci. 2007 Apr. 1100:455-69. [Medline].

  3. Zhao N, Hao F, Qu T, Zuo YG, Wang BX. A novel mutation of the WRN gene in a Chinese patient with Werner syndrome. Clin Exp Dermatol. 2008 May. 33(3):278-81. [Medline].

  4. Davis T, Brook AJ, Rokicki MJ, Bagley MC, Kipling D. Evaluating the Role of p38 MAPK in the Accelerated Cell Senescence of Werner Syndrome Fibroblasts. Pharmaceuticals (Basel). 2016 Apr 28. 9 (2):[Medline].

  5. Hisama FM, Kubisch C, Martin GM, Oshima J. Clinical utility gene card for: Werner syndrome. Eur J Hum Genet. 2012 Jan 18. [Medline].

  6. Saha B, Lessel D, Nampoothiri S, Rao AS, Hisama FM, Peter D, et al. Ethnic-Specific WRN Mutations in South Asian Werner Syndrome Patients: Potential Founder Effect in Patients with Indian or Pakistani Ancestry. Mol Genet Genomic Med. 2013 May 1. 1(1):7-14. [Medline]. [Full Text].

  7. Mansur AT, Elçioglu NH, Demirci GT. Werner syndrome: clinical evaluation of two cases and a novel mutation. Genet Couns. 2014. 25(2):119-27. [Medline].

  8. Barrios Sanjuanelo A, Munoz Otero C. [Atypical Werner syndrome: Atypical progeroid syndrome: A case report.]. An Pediatr (Barc). 2010 May 7. [Medline].

  9. Friedrich K, Lee L, Leistritz DF, et al. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations. Hum Genet. 2010 May 5. [Medline].

  10. Pirzio LM, Pichierri P, Bignami M, Franchitto A. Werner syndrome helicase activity is essential in maintaining fragile site stability. J Cell Biol. 2008 Jan 28. 180(2):305-14. [Medline].

  11. Kyng KJ, Bohr VA. Gene expression and DNA repair in progeroid syndromes and human aging. Ageing Res Rev. 2005 Nov. 4(4):579-602. [Medline].

  12. Doh YJ, Kim HK, Jung ED, Choi SH, Kim JG, Kim BW, et al. Novel LMNA gene mutation in a patient with Atypical Werner's Syndrome. Korean J Intern Med. 2009 Mar. 24(1):68-72. [Medline].

  13. McKenna T, Sola Carvajal A, Eriksson M. Skin Disease in Laminopathy-Associated Premature Aging. J Invest Dermatol. 2015 Jul 29. [Medline].

  14. Goto M, Ishikawa Y, Sugimoto M, Furuichi Y. Werner syndrome: a changing pattern of clinical manifestations in Japan (1917~2008). Biosci Trends. 2013 Feb. 7(1):13-22. [Medline].

  15. Kawai T, Nozato Y, Kamide K, Onishi M, Yamamoto-Hanasaki H, Tatara Y, et al. Case report of a long-surviving Werner syndrome patient with severe aortic valve stenosis. Geriatr Gerontol Int. 2012 Jan. 12(1):174-5. [Medline].

  16. Takada-Watanabe A, Yokote K, Takemoto M, Fujimoto M, Irisuna H, Honjo S, et al. A case of Werner syndrome without metabolic abnormality: implications for the early pathophysiology. Geriatr Gerontol Int. 2012 Jan. 12(1):140-6. [Medline].

  17. 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. [Medline]. [Full Text].

  18. Mitamura Y, Azuma S, Matsumoto D, Takada-Watanabe A, Takemoto M, Yokote K, et al. Case of sarcomatoid carcinoma occurring in a patient with Werner syndrome. J Dermatol. 2016 Apr 14. [Medline].

  19. Massip L, Garand C, Paquet ER, et al. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J. 2010 Jan. 24(1):158-72. [Medline].

  20. Solek-Pastuszka J, Zagrodnik-Ulan E, Plonka T, et al. Pregnancy complicated by Werner syndrome. Acta Obstet Gynecol Scand. 2011 Feb. 90(2):201-2. [Medline].

  21. Wang Z, Xu Y, Tang J, Ma H, Qin J, Lu C, et al. A polymorphism in Werner syndrome gene is associated with breast cancer susceptibility in Chinese women. Breast Cancer Res Treat. 2009 Feb 10. [Medline].

  22. Oshitari T, Kitahashi M, Mizuno S, Baba T, Kubota-Taniai M, Takemoto M, et al. Werner syndrome with refractory cystoid macular edema and immunohistochemical analysis of WRN proteins in human retinas. BMC Ophthalmol. 2014 Mar 12. 14:31. [Medline]. [Full Text].

Werner syndrome.
Werner syndrome.
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