He Werner's syndrome Is a pathology of genetic origin that produces an early or accelerated aging at an early age (Oshima, Sidorova, Monnat, 2016).
Although at clinical level, it presents a variable course and is characterized by the development of juvenile cataracts, short stature, obesity, cutaneous atrophy, among other signs of aging (Labbé et al., 2012).
At the etiological level, Werner's syndrome occurs as a consequence of a specific mutation in the WRN gene, located in the Chromosome 8 , although Other factors could also be involved (Hyun, Choi, Stevnsner and Ahn, 2016).
As for the diagnosis, this is based fundamentally on the cardinal clinical aspects, based on the diagnostic criteria proposed by the International Registry of Werner Syndrome. In addition, it is considered infrequent during childhood or adolescence, becoming Early adulthood (Sanjuanelo and Otero, 2012).
At present, there is no treatment for Werner's syndrome. The life expectancy of those affected does not usually exceed 50 years of age, Due to the progress of organic aging.
However, there are several therapeutic approaches for the improvement of some symptoms, Cataracts, skin grafts, cardiac by-pass, etc. (Gragera, Rojas and Salas Campo, 2006).
In general, the main causes of death in Werner syndrome are related to the development of tumors, atherosclerotic pathologies Or cerebral infarcts (Yamamoto et al., 2015).
Characteristics of Werner's syndrome
Werner's syndrome is a disorder characterized by the exponential development of features associated with biological aging Premature (Genetics Home reference, 2016).
In addition, this syndrome is classified into a group of pathologies called Progeria , Characterized by the appearance of signs and symptoms of Early or accelerated aging (Sanjuanelo and Otero, 2010).
Within the programs, two fundamental subtypes, adult and child, have been described. In the case of the child's clinical form, this disorder Is called Hutchinson-Gilford syndrome, while the adult form is called Werner syndrome (SW) (Sanjuanelo and Otero, 2010).
Aging is a physiological phenomenon or process, however, theories about its biological mechanisms and clinical characteristics are Multifactorial. However, in a general way, all these refer to the existence of intrinsic factors, related to genetics or Oxidative stress, or to the presence of extrinsic factors, related to the lifestyles And environmental elements (Jaeger, 2011).
Under normal conditions, physiological and anatomical changes related to aging begin to occur several years before their External manifestations that begin to be evident around the age of 40 and progress gradually until the death of the individual (Jaeger, 2011).
However, under various pathological conditions, such as Werner's syndrome, the decline of organic functions, tissues and appearance (Jaeger, 2011), may appear prematurely associated with genetic alterations.
Thus, Werner's syndrome (SW) was initially described by specialist German ophthalmologist Carl Wilhem Otto Werner. This is the theme Center of his doctoral thesis to the description of 4 cases with signs of premature aging (Gragera, Rojas and Salas Campo, 2006).
Specifically, Werner reported several cases belonging to the same family, whose members, aged between 31 and 40, Showed small stature, bilateral juvenile cataracts and other signs of senescence, such as gray hair (Oshima, Sidorova, Monnat, 2016).
However, it is not until 1934, when the term Werner's syndrome is used as a clinical entity. This one was used by Oppenheimer and Kugel to make Reference to a new case, whereas Tannhauserin, in 1945, provides a comprehensive clinical review of this pathology (Oshima, Sidorova, Monnat, 2016).
Later, thanks to the advance of research methods, the genetic factor involved in its etiology was identified in 1996 (Yu et al., 1996; Oshima, Sidorova, Monnat, 2016).
Finally, as we have pointed out earlier, Werner syndrome is currently defined as a rare disorder characterized by The progressive development of an abnormally accelerated aging process (National Organization for Rare Disorders, 2015).
In most cases, Werner's syndrome is identified around the third or fourth decade of life, ie between 30 and 40 years of age. age. However, some clinical findings, which we will describe below, may already be present since adolescence or the beginning of the adulthood.
About us
Many of the institutions and authors who have focused their studies on the investigation of Werner syndrome, point out that it is a pathology Sporadic or rare genetics (Orphanet, 2012).
In general, all medical conditions related to precocious aging are uncommon in the general population and, as a consequence, there are Few statistical studies that examine its prevalence and incidence (Sanjuanelo and Muñoz Otero, 2010).
However, up to 2002, more than 1,300 Werner's syndrome have been reported in the medical and scientific literature (Sanjuanelo and Muñoz Otero, 2010).
In addition, it has been estimated that Werner's syndrome can affect approximately one person per 200,000 individuals residing in the United States (Genetics Home Reference, 2016).
Although this pathology, product of a specific genetic alteration, can suffer any type of person (Genetics Home Reference, 2016).
Apart from this, it is more frequent in Japan. The majority of clinical cases that are described came from this geographical region (Genetics Home Reference, 2016).
In addition, it is estimated that affects one person in every 20,000-40,000 inhabitants (Genetics Home Reference, 2016).
Signs and symptoms
All clinical findings associated with Werner's syndrome are related to premature aging, however, they may vary depending on the Time of onset and clinical course of this pathology (National Organization for Rare Disorders, 2015 Orphanet, 2016, Oshima, Sidorova and Monnat, 2016):
Puberty and Adolescence
In general, anomalies are not usually identified during the postnatal or childhood stage. It is most common to identify this disease during puberty or adolescence, due to the presence of slow growth or development.
In most individuals, it is possible to identify a weight or short stature in relation to that expected for their gender and age group.
Therefore, confirmation of the diagnosis at this stage is uncommon, although the initial delay of biological growth and development is usually followed Of other types of alterations related to the exponential deterioration of the organism.
Early Childhood
Around 20-30 years of age, it is possible to identify more evident signs of precocious aging.
In addition to the absence of a normalized growth stage during adolescence, a number of age-related alterations are added: ophthalmologic, cutaneous anomalies, etc.
Some of the most common include:
- Bilateral juvenile waterfalls : Cataracts, is a type of ophthalmological pathology in which there is an opacity of the Crystalline lens of the eye, which hinders defined vision. Usually, this disorder is associated with aging and the advanced ages, however, There are several cases of early presentation associated with genetic alterations.
- Canicie : The term canicie is used to refer to the absence or progressive loss of hair pigmentation. In the People with Werner's syndrome are often observed to have gray or white hair prematurely.
- Alopecia : The term alopecia is used to refer to hair loss, commonly known as baldness. Although Usually associated with a genetic predisposition and aging, in Werner syndrome can also be seen prematurely.
- Loss of adipose tissue And muscular atrophy: As in older ages, it is very common to see a loss Significant weight loss associated with muscle and fat loss. In addition, along with these signs of degeneration it is also possible to identify one Progressive bone loss and soft tissue hardening or calcification, such as tendon structures resulting from accumulation Abnormal calcium.
- Skin Regeneration : The cutaneous anomaly is one of the most common clinical findings in Werner's syndrome. The most common signs are related to hyperpigmentation (development of spots and increased coloration), hypopigmentation (skin discoloration), blisters and redness resulting from widening of blood bases (telangiectasia), thickening of localized areas, especially in the elbows or knees ( Hyperkeratosis) or development of open ulcers at the superficial level.
In addition to these signs and symptoms, Werner's syndrome causes important medical complications, also related to premature aging And accelerated (National Organization for Rare Disorders, 2015, Sanjuanelo and Muñoz Otero, 2010):
- Hypogonadism : In both men and women it is possible to observe a deficient production of sex hormones, much of it The affected is associated with the development of infertility.
- Mellitus diabetes : Deficient insulin synthesis is another of the most common medical symptoms, so the amount of glucose Blood is poorly regulated, requiring medical therapy.
- Osteoporosis : The reduction of the bone density can be reduced pathologically, until reaching an exaggerated fragility in different bones.
- Neoplasms : The overproduction or abnormal accumulation of cells can give rise to the development of tumors or neoplasias, both benign As carcinogenic.
- Neurological disorders : In this area, alterations are mainly related to the reduction of reflexes or development Of paresthesias.
- Heart alterations : The most frequent anomalies are related to cardiac abnormalities and other alterations, which occur Mainly with heart failure.
Causes
The cause of Werner's syndrome is genetic, it is specifically associated to mutations in the WRN gene, located on chromosome 8, in the Location 8p-12 (Genetics Home Reference, 2015).
Although different researchers report that 90% of patients diagnosed with Werner syndrome have an identified mutation, it is not possible to identify significant changes at the genetic level (Sanjuanelo and Otero, 2010).
The WRN gene is responsible for generating biochemical instructions for the production of proteins that play a prominent role in maintenance tasks And repair of DNA (Genetics Home Reference, 2015).
In general, cells with this type of protein deficit, have a reduced division rate or lose this capacity, so they appear Development problems. (Genetics Home Reference, 2015).
Diagnosis
The diagnosis of Werner's syndrome is eminently clinical, through the analysis of family and individual medical history and physical examination, Is to identify the central medical traits
In general, the diagnostic criteria of the International Registry of Werner Syndrome are used, in them, the cardinal signs refer A (Genetics Home Reference, 2015):
- Presence of bilateral cataracts.
- Alter skin (atrophic and sclerotic skin, alterations in coloration, ulcers, etc.).
- Low or reduced height.
- Premature aging.
- Fine or gray hair.
In addition, other additional signs and symptoms such as diabetes , Hypogonadism, osteoporosis, soft tissue calcification, Neoplasms, or premature atherosclerosis (Genetics Home Reference, 2015).
In addition, the genetic study is recommended, to identify possible specific mutations and hereditary patterns associated with this pathology.
Is there an effective treatment?
As we pointed out in the introduction, Werner syndrome is a degenerative disease for which there is no identified cure. In most of In the cases, life expectancy does not reach ages greater than 50 years (Gragera, Rojas and Salas Campo, 2006). Stroke, or the development of tumors (Gragera, Rojas and Salas Campo, 2006).
Therefore, the treatment used is mainly symptomatological. Different medical complications are treatable at the pharmacological level or Surgery, such as cataracts, diabetes or cardiac abnormalities.
On the other hand, in the case of cutaneous diseases, it is especially important to carry out regular check-ups and inspections with the aim of avoiding infections Which aggravate the clinical condition of the patient and, in addition, put their survival at risk.
In addition, physical therapy and maintenance of routine activity are essential for muscular atrophy, with the aim of prolonging as much as possible In time the autonomy of the person affected.
References
- Gragera, A., Fernandez Rojas, J., & Salas Campos, E. (2006). Adult Progeria (Werner's syndrome). Follow up of 2 cases from Primary Care. SEMERGEN , 410-414.
- Hyun, M., Choi, S., Stevnsner, T., & Ahn, B. (2016). The Caenorhabditis elegansWerner syndrome protein participates in DNA The Caenorhabditis
ElegansWerner syndrome protein participates in DNA double-strand breaks. Cellular Signaling , 214-233. - Jaeger, C. (2011). Physiology of aging. EMC .
- Labbé et al; . (2012). The Werner syndrome gene product (WRN): are pressor of hypoxia-inducible factor-1 activity. E X P ERIMENTALCELLRESEARCH , 1620-1632.
- NIH. (2016). Werner syndrome . Retrieved from the Genetics Home Reference.
- NORD. (2015). Werner Syndrome . Retrieved from the National Organization for Rare Disorders:.
- Orphanet. (2012). Werner syndrome . Obtained from Orphanet.
- Oshima, J., Sidorova, J., & Monnat, R. (2016). Werner syndrome: clinical features, pathogenesis and potential therapeutic interventions. Ageing Research Reviews .
- Sanjuanelo, A., & Muñoz Otero, c. (2010). Atypical Werner syndrome: atypical progeroid syndrome. An Pediatr (Barc) , 94-97.
- Yamamoto et al. (2015). A case of Werner's syndrome with cardiac syndrome X and heart failure with preserved ejection fraction. Journal of Cardiology Cases , 195-198.