Werner syndrome




Werner's syndrome (WS) is a rare genetic disorder characterized by premature aging and predisposition to cancer (tumor). The first sign is the lack of growth during puberty associated with the appearance of other significant characteristics:

  • hair loss and graying
  • hoarseness and scleroderma-like skin changes
  • cataract to both eyes (bilateral)
  • type 2 diabetes
  • hypogonadism
  • skin ulcers
  • osteoporosis

People with Werner syndrome have a shortened life expectancy (45-55 years), although the prognosis depends on the aging disorders present and their severity. The most common causes of death are myocardial infarction and cancer.

The prevalence of Werner syndrome varies according to the level of consanguinity of the populations.In Japan, for example, it is between 1 case in 20,000 and 1 case in 40,000; in Sardinia it is 1 in 50,000, while in the United States it is about 1 in 200,000. In other populations, the prevalence is unknown but is estimated to be between 1 in 380,000 and 1 in 1,000,000

In Italy, Werner syndrome is included in the "list of rare diseases exempt from the cost of the ticket (Decree of the President of the Council of Ministers of 12 January 2017, Annex 7) with the code RC0060.

For other information (diagnosis and treatment centers, patient associations, etc.) on the syndrome, it is possible to contact the Rare Diseases Toll-Free Telephone (TVMR) 800.89.69.49. The number - with national coverage and free from landlines and mobile phones - is active from Monday to Friday from 9:00 to 13:00.



People with Werner syndrome have specific characteristics and disorders affecting the organs and systems of the body which include:

"Bird" Facies

The aspect of the face is very characteristic and it is said, in fact, a bird shape due to the beak shape of the nose.


People with Werner's syndrome can have different forms of atherosclerosis; the most serious is coronary artery arteriosclerosis which can lead to myocardial infarction, which, along with cancer, is the most common cause of death.


People with Werner syndrome have a higher risk of developing carcinomas and even very rare sarcomas.


Osteoporosis occurs in an unusual form because it mainly affects the long bones. The total or partial fracture of the bone (osteolytic lesions) characteristic of the finger joints is evidenced on radiographs.

Nervous system

There are conflicting opinions regarding the type of brain involvement. Indeed, people with Werner's syndrome may have central nervous system complications associated with arteriosclerosis, but they do not appear to be particularly susceptible to Alzheimer's disease, typically linked to the normal aging process. decrease in reasoning, attention, memory and language skills (cognitive deficits).

Decline in fertility

Fertility appears to decline soon after sexual maturity (puberty). This is associated in males with testicular atrophy and in females with the probable accelerated loss of primordial follicles in the ovaries, although data are scarce. Premature menopause is common in women, as are multiple miscarriages, but pregnancies have also been reported. success: Men have fathered children, usually at a younger age than the general population.



In the majority of cases studied, Werner's syndrome depends on mutations in the gene WRN(located on chromosome 8p11-12) which contains specific information for the production of a protein involved in maintaining the integrity of the genome (the set of all genes present in DNA).

The disease is transmitted in an autosomal recessive manner: for the disease to manifest itself it is necessary to inherit two defective genes from the parents, one from the mother and one from the father. If you inherit just one mutated gene, you become a healthy carrier and don't develop the disease. A child who has two parents who are healthy carriers of the mutated gene therefore has a 25% chance of being sick and a 50% chance of being a child. healthy carrier.

The gene mutation can be caused by so-called nonsense mutations, that is, by the change of a molecule (the nucleotide), by insertions and / or deletions (loss of genetic material) of the WRN gene. Mutations in the WRN gene have been found in approximately 90% of confirmed (diagnosed) cases of Werner syndrome. The remaining 10% of cases are due to other causes (such as gene mutation LMNA) and is classified as atypical Werner syndrome.



The assessment of the disease (diagnosis) is based on the presence of all the main disorders (symptoms) and at least two additional ones. The observation of the disorders is followed by genetic analysis, with the search for mutations / deletions in the WRN gene.

The main complaints are:

  • cataract in both eyes (present in 99% of cases)
  • premature graying and / or hair thinning of the scalp (100% of cases)
  • characteristic dermatological disease (96% of cases)
  • short (95% of cases)

About 91 percent of people with Werner's syndrome have all four major disorders.

Additional signs and disorders (symptoms) include:

  • thin limbs (present in 98% of cases)
  • typical facial features (96% of cases)
  • osteoporosis (91% of cases)
  • change of voice (89% of cases)
  • hypogonadism (80% of cases)
  • type 2 diabetes mellitus (71% of cases)
  • soft tissue calcification (67% of cases)
  • tumors (44% of cases)
  • arteriosclerosis (30% of cases)

The average age at which the disease is ascertained (diagnosed) is around 35, given that in many people some of the main ailments do not manifest themselves until around 30-40 years of age.

Molecular genetic tests

The analysis of the sequence of the WRN gene is performed first and is aimed at identifying variants capable of causing disease (pathogenetic). A set of multiple genes (multigene panel) that includes the WRN gene and others of interest may also be considered (doctors determine which multigene panel is most likely to identify the genetic cause of Werner syndrome). More comprehensive testing (if available), including exome sequencing (set of all genes in DNA that contain information for protein production) and genome sequencing, may be indicated if monogenic testing and the search for Gene deletions (and / or the use of a multigene panel that includes the WRN gene) do not confirm the presence of Werner syndrome in an individual who, on the other hand, has all its characteristics.

Protein analysis

In some unusual cases, protein analysis can be useful when both WRN alleles cannot be identified by sequence analysis. In this case we proceed by Western blot or immunoblot analysis, a biochemical technique that allows to identify a specific protein in a mixture of proteins, and which in the specific case show the absence of the normal WRN protein.



To date, there is no cure for Werner syndrome. The patient is taken care of by a group of specialists (multidisciplinary team) who deal with the alterations related to the syndrome (skin ulcers, diabetes, cardiovascular diseases, cataracts) to activate any useful treatments for the prevention of further complications, for example a balanced diet , regular exercise and an adequate lifestyle in general.

The most appropriate treatments for any disorders that may appear include:

  • aggressive treatment of skin (cutaneous) ulcers, with standard or innovative techniques. Bosentan has been shown to be effective in treating digital ulcers in people with systemic sclerosis and its use has recently been reported to be beneficial in people with Werner syndrome as well.
  • utilization of pioglitazone and sitagliptin, effective in the control of type 2 diabetes mellitus
  • use of drugs that lower cholesterol, in case of abnormal blood levels
  • surgical treatment of ocular cataracts
  • cancer treatment

In addition to psychological counseling for patients and their families, avoiding smoking, exercising regularly and controlling body weight is recommended to reduce the risk of atherosclerosis.

Main recommended checks

The main checks to be performed include:

  • screening for type 2 diabetes mellitus, at least once a year
  • lipid profile, Once a year
  • tests for the identification of malignant tumors common in Werner syndrome, once a year; tests for the identification of other skin manifestations, once a year
  • eye examination for cataracts, Once a year
  • control of any disorders associated with angina pectoris, to alterations of the peripheral arteries or to alterations of the cerebral vessels
Atypical Werner syndrome

Atypical Werner syndrome

Atypical Werner syndrome (aWS) affects a heterogeneous group of people with characteristics similar to those of classic Werner syndrome but not associated with gene mutations WRN. A subgroup of atypical Werner syndrome is due to the gene mutation LMNA, the same gene associated with the onset of the disease Hutchinson-Gilford syndromic progeria.

Atypical Werner's syndrome is transmitted in form autosomal dominant. This means that it is enough to inherit the defective gene from just one parent to develop the disease.

Recently, other causes for aWS and related modes of transmission have also been discovered.

Symptoms and characteristics

Atypical Werner syndrome manifests itself with:

  • rapid aging
  • short
  • hair thinning
  • "bird-shaped" face
  • thinning of the skin (skin atrophy)
  • muscle changes (myopathy)
  • osteoporosis
  • arteriosclerosis

Compared to Werner syndrome, it has an earlier onset (appears earlier) and progresses more rapidly. Cataracts are often not present.



Oshima J, Martin GM, Hisama FM. Werner Syndrome. 2002 Dec 2 [Updated 2016 Sep 29]. In: Adam MP, Ardinger HH, Pagon RA, et al., Editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019 (English)

In-depth link

In-depth link

For Werner's syndrome

National Institutes of Health (NIH). Genetic and Rare Diseases Information Center (GARD). Werner syndrome (English)

Johns Hopkins University. OMIM - Online Mendelian Inheritance in Man. Werner Syndrome (English)

National Institutes of Health (NIH). National Library of Medicine. Genetics Home Reference (GHR). Werner syndrome (English)

For atypical Werner syndrome

National Institutes of Health (NIH). Genetic and Rare Diseases Information Center (GARD). Atypical Werner syndrome (English)

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