Werner Syndrome Clinical Presentation

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Feb 28, 2012
 

History

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.[4] 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.[11]

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Physical

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

  • 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

  • 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

  • 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

  • Carcinomas of the thyroid and other organs
  • Hematologic malignancies
  • Sarcomas
  • Meningiomas
  • Cutaneous malignancies, including malignant melanoma
  • 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
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Causes

WS is a genetic disorder. See Pathophysiology.

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Contributor Information and Disclosures
Author

Camila K Janniger, MD  Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

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

Disclosure: Nothing to disclose.

Coauthor(s)

Anna Wozniacka, MD, PhD  Adjunct Lecturer, 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

Disclosure: Nothing to disclose.

Specialty Editor Board

Franklin Flowers, MD  Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

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

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

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

Disclosure: Nothing to disclose.

References

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  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. Apr 2007;1100:455-69. [Medline].

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

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  10. 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. Jan 2012;12(1):174-5. [Medline].

  11. 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. Jan 2012;12(1):140-6. [Medline].

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

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

  14. 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. Feb 10 2009;[Medline].

  15. Ariyoshi K, Suzuki K, Goto M, Watanabe M, Kodama S. Increased Chromosome Instability and Accumulation of DNA Double-strand Breaks in Werner Syndrome Cells. J Radiat Res (Tokyo). May 2007;48(3):219-31. [Medline].

  16. Barak Y, Sirota P, Kimhi R, Slor H. Werner's syndrome (adult progeria): an affected mother and son presenting with resistant psychosis. Compr Psychiatry. Nov-Dec 2001;42(6):508-10. [Medline].

  17. Bohr VA, Souza Pinto N, Nyaga SG, Dianov G, Kraemer K, Seidman MM, et al. DNA repair and mutagenesis in Werner syndrome. Environ Mol Mutagen. 2001;38(2-3):227-34. [Medline].

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  20. Harrigan JA, Wilson DM, Prasad R, Opresko PL, Beck G, May A, et al. The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase beta. Nucleic Acids Res. Jan 30 2006;34(2):745-54. [Medline].

  21. Hrabko RP, Milgrom H, Schwartz RA. Werner's syndrome with associated malignant neoplasms. Arch Dermatol. Feb 1982;118(2):106-8. [Medline].

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  23. Machwe A, Xiao L, Orren DK. Length-dependent degradation of single-stranded 3' ends by the Werner syndrome protein (WRN): implications for spatial orientation and coordinated 3' to 5' movement of its ATPase/helicase and exonuclease domains. BMC Mol Biol. 2006;7:6. [Medline].

  24. Navarro CL, Cau P, Levy N. Molecular bases of progeroid syndromes. Hum Mol Genet. Oct 15 2006;15 Spec No 2:R151-61. [Medline].

  25. Opresko PL, Laine JP, Brosh RM Jr, Seidman MM, Bohr VA. Coordinate action of the helicase and 3' to 5' exonuclease of Werner syndrome protein. J Biol Chem. Nov 30 2001;276(48):44677-87. [Medline].

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  27. Shibuya H, Kato A, Kai N, Fujiwara S, Goto M. A case of Werner syndrome with three primary lesions of malignant melanoma. J Dermatol. Sep 2005;32(9):737-44. [Medline].

 
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