Werner Syndrome

Werner syndrome is a rare genetic disorder characterized by rapid aging. Individuals with this syndrome typically grow and develop normally until they reach puberty. The age of onset of Werner syndrome is variable, but an early sign is the lack of a teenage growth spurt, which results in short stature. Affected individuals typically have a characteristic facial appearance described as "bird-like" by the time they reach their thirties. People affected by Werner syndrome usually live into their late forties or early fifties.

Location of the WRN gene, Source: NIH ^[1]

Other Names

• Adult Progeria

Signs and Symptoms

In addition to short stature, other signs and symptoms of Werner syndrome usually appear when affected people are in their twenties or thirties and include:

• Loss and graying of hair
• Hoarseness
• Thickening of the skin
• Cloudy lenses in the eye (cataracts)
• "Bird-like" faces
• Thin arms and legs
• Thick trunk
• Type 2 Diabetes
• Diminished fertility
• Severe hardening of the arteries (arteriosclerosis)
• Thinning bones (osteoporosis)
• Cancer

Causes

Werner syndrome is cause by a genetic mutation; thus it is a inherited disease. The inheritance pattern is autosomal recessive, which means the gene is not carried on the X or Y sex chromosomes and that the disorder occurs only when someone inherits two copies of the gene.

Mutations in the WRN gene cause Werner syndrome.^[2]

The WRN gene codes for the Werner protein. This protein performs several tasks related to the genetic material DNA. Werner protein assists in maintaining and replicating DNA during cell division. The disorder is inherited and transmitted as an autosomal recessive trait. Cells from WS patients have a shorter lifespan in culture than do normal cells. The gene for Werner disease (WRN) was mapped to chromosome 8. It is a predicted helicase belonging to the RecQ family. The exact molecular role of the WRN protein in Werner syndrome therefore remains to be proven, as does any role it might have in the aging process in general. The protein is likely to be involved in the response to DNA damage during replication, as well as in the replication and transcription processes. The disease is connected with excessive synthesis of collagen types I and III, which is dependent on elevated messenger RNA (mRNA) levels. The collagenase level is also increased several times. This increase in collagen cause connective tissue disorders.^[3]

Treatment

There is no cure for Werner syndrome. Treatment centers around symptomatic management.

Prognosis

People with Werner syndrome usually live into their late forties or early fifties. Heart attack and cancer are the most common causes of death.

Epidemiology

Incidence

Werner syndrome is a rare disorder. The estimated incidence is 1 case in 1 million individuals. Werner syndrome is more common in Japan and Sardinia than in other regions. About 1000 cases are reported in the world; more than 800 of these cases are in Japan.

References

1. ↑ http://ghr.nlm.nih.gov/gene=wrn
2. ↑ Martin GM.Genetics and the pathobiology of ageing. Philos Trans R Soc Lond B Biol Sci. 1997 Dec 29;352(1363):1773-80. ]Abstract | Full Text
3. ↑ Muftuoglu M, Kusumoto R, Speina E, Beck G, Cheng W, et al. 2008 Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair. PLoS ONE 3(4): e1918 Full Text

External Links

Genetics Home Reference NCBI Univ. of Washington, Dept. of Pathology: Werner Syndrome