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Werner's syndrome

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Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

Synonyms: adult premature ageing syndrome, adult progeria

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What is Werner's syndrome?

Werner's syndrome (WS) is an extremely rare, autosomal recessive, systemic disease which is associated with features of premature aging and cancer predisposition. The syndrome is named after C. W. Otto Werner, a German physician (1879-1936).


Interest in Werner's syndrome (WS) is fuelled in part by the observation that transcription aberrations in WS are similar to those found in normal ageing.1 In WS, the gene defect is known to affect WRN (found on chromosome 8) encoding Werner protein, a nuclear protein with helicase and exonuclease activity important in maintaining and repairing DNA, particularly where double-strand breaks occur.2 3 WRN gene mutations encode an abnormally shortened Werner protein.

More than 50 different disease-causing mutations in the WRN gene have been identified in WS patients.

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How common is Werner's syndrome? (Epidemiology)

  • It is extremely rare, with only approximately 1,300 cases reported worldwide since 1916, with 1,000 of those coming from Japan.4

  • A prevalence of 1/200,000 US population is contrasted with 1/20-40,000 Japanese population (ie 10-20 x more common).

  • In Japan the frequency of heterozygote carriers of the condition within the general population is estimated as 1/180.3

Symptoms of Werner's syndrome (presentation)

  • Typically, individuals grow normally until puberty.5

  • The first symptom is the lack of a teen growth spurt.

  • Early findings (observed in the 20s) are loss and greying of hair, hoarseness and scleroderma-like skin changes.

  • This is followed (typically in the 30s) by bilateral cataracts, type 2 diabetes mellitus, hypogonadism, refractory skin ulcers and osteoporosis.

  • Most will present to dermatologists or ophthalmologists in the first instance.

Typical signs and symptoms

Suggested diagnostic criteria:6

  • Bilateral cataracts.

  • Characteristic skin: tight, atrophic, pigmentary changes, ulceration, hyperkeratosis.

  • 'Bird-like' facies.

  • Short stature.

  • Premature greying and/or balding.

Other signs and symptoms

  • Type 2 diabetes mellitus.

  • Hypogonadism and decreased fertility.

  • Osteoporosis.

  • Osteosclerosis of distal phalanges of fingers and/or toes.

  • Soft-tissue calcification.

  • Premature arteriosclerosis.

  • Neoplasms: mesenchymal (sarcomas), unusual or multiple types or sites.

  • High-pitched, squeaky or hoarse voice.

  • Flat feet.

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Differential diagnosis7

  • Atypical Werner's syndrome (WS) - small subset with normal WRN protein. Earlier age of onset and faster progression compared with classic WS.

  • Hutchinson-Gilford progeria syndrome most closely resembles WS. Neonates with WS appear normal but fail to thrive during their first year, with connective tissue abnormalities becoming apparent in the second and third year, and death usual between 6-20 years.

  • Early-onset type 2 diabetes mellitus with secondary vascular and skin complications.

  • Myotonic dystrophy - in view of the young adult-onset cataracts - but other features are different and onset is usually in adulthood.

  • Scleroderma, mixed connective-tissue disorders, lipodystrophy and Charcot-Marie-Tooth syndrome have some skin features similar to WS.

Diagnosing Werner's syndrome (investigations)7

  • Urinary and serum hyaluronic acid is increased in most individuals.

  • Sequence analysis of the WRN coding region detects mutations in both alleles for approximately 90%.

  • Western blot - usually absent Werner protein.

Associated diseases

Werner's syndrome (WS) is associated with several diseases of old age including:

Management of Werner's syndrome

Early recognition of the syndrome is helpful, as screening for malignancies and associated diseases such as diabetes may then be performed on a regular basis.
There is no specific treatment available for Werner's syndrome (WS), although surgical intervention and hyperbaric oxygen therapy may be of use in the treatment of refractory skin ulcers.5


  • Treatment of diabetes - glitazones are thought to be particularly effective.8

  • Cholesterol lowering where lipid profile is abnormal.9

  • Standard treatments for malignancies and ischaemic heart disease.

  • Preliminary mouse studies suggest vitamin C supplementation may be beneficial.10

  • New studies have demonstrated involvement of particular genes and considered activation of P13K/AKT activation to improve the possible future benefits of stem cell based therapy. 11


  • Specific surgical procedures may be required to treat complications such as cataracts and contractures.

Genetic counselling

Fertility is much reduced but there are recorded instances of individuals of both sexes having children.

  • Obligate carrier status of all affected individual's children.

  • For siblings of an affected individual, there is a 1 in 4 risk of having the disease and a 1 in 2 risk of carrier status as a sibling.

  • Relatives of affected individuals should have increased cancer surveillance.3


The life span of individuals with Werner's syndrome (WS) is reduced. Death previously occurred on average in the mid-40s, commonly as a result of malignancy or myocardial infarction.4

However, recent studies suggest an increase in the average age of death to the late 50s with fewer dying from vascular events. 12

Prevention of Werner's syndrome

Prenatal screening may be available to parents who are considered at high risk of having an affected child.

Further reading and references

  1. Kyng KJ, Bohr VA; Kyng KJ, Bohr ; Gene expression and DNA repair in progeroid syndromes and human aging. Ageing Res Rev. 2005 Nov;4(4):579-602. Epub 2005 Oct 24.
  2. Lan L, Nakajima S, Komatsu K, et al; Accumulation of Werner protein at DNA double-strand breaks in human cells. J Cell Sci. 2005 Sep 15;118(Pt 18):4153-62. Epub 2005 Sep 1.
  3. Muftuoglu M, Oshima J, von Kobbe C, et al; The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis. Hum Genet. 2008 Sep 23.
  4. Yamamoto K, Imakiire A, Miyagawa N, et al; A report of two cases of Werner's syndrome and review of the literature. J Orthop Surg (Hong Kong). 2003 Dec;11(2):224-33.
  5. Werner syndrome, Online Mendelian Inheritance in Man (OMIM)
  6. Nakura J, Wijsman EM, Miki T, et al; Homozygosity mapping of the Werner syndrome locus (WRN). Genomics. 1994 Oct;23(3):600-8.
  7. Gene review; Werner syndrome. Last updated 2007; funded by NIH
  8. Hattori S, Kasai M, Namatame T, et al; Pioglitazone treatment of insulin resistance in a patient with Werner's syndrome. Diabetes Care. 2004 Dec;27(12):3021-2.
  9. Leistritz DF, Hanson N, Martin GM, et al; Werner Syndrome
  10. Janniger CK et al; Werner Syndrome, Medscape, Jan 2010
  11. Tu J, Wan C, Zhang F, et al; Genetic correction of Werner syndrome gene reveals impaired pro-angiogenic function and HGF insufficiency in mesenchymal stem cells. Aging Cell. 2020 May;19(5):e13116. doi: 10.1111/acel.13116. Epub 2020 Apr 22.
  12. Lifetime extension and the recent cause of death in Werner syndrome: a retrospective study from 2011 to 2020; Orphanet Journal of Rare Disease

Article history

The information on this page is written and peer reviewed by qualified clinicians.

  • Next review due: 19 Sept 2028
  • 21 Sept 2023 | Latest version

    Last updated by

    Dr Pippa Vincent, MRCGP

    Peer reviewed by

    Dr Doug McKechnie, MRCGP
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