viernes, 27 de noviembre de 2015

genetic mutations: Werner Syndrome


Genetic mutations: Werner Syndrome

Werner Syndrome may also be characterized by development of a distinctive high-pitched voice; eye abnormalities, including premature clouding of the lenses of the eyes (bilateral senile cataracts); and certain endocrine defects, such as impaired functioning of the ovaries in females or testes in males (hypogonadism) or abnormal production of the hormone insulin by the pancreas and resistance to the effects of insulin (non-insulin-dependent diabetes mellitus). In addition, individuals with Werner syndrome may develop progressive thickening and loss of elasticity of artery walls (arteriosclerosis). Affected blood vessels typically include the arteries that transport oxygen-rich (oxygenated) blood to heart muscle (coronary arteries). Some affected individuals may also be susceptible to developing certain benign (noncancerous) or malignant tumors. Progressive arteriosclerosis, malignancies, and/or associated abnormalities may result in potentially life-threatening complications by approximately the fourth or fifth decade of life. Werner syndrome is inherited as an autosomal recessive trait.
Signs and  Symptoms

Children with Werner Syndrome often appear unusually thin and, during late childhood, have an unusually slow growth rate. In addition, there is absence of the growth spurt typically seen during adolescence. Affected individuals typically reach their final height by approximately 13 years of age. However, adult height may be reached as early as at age 10 or as late as at age 18. Weight is also unusually low, even relative to short stature.
Before age 20, most individuals with Werner Syndrome develop early graying and whitening of the scalp hair (canities). By about 25 years of age, affected individuals may experience premature loss of scalp hair (alopecia) as well as loss of the eyebrows and eyelashes. In addition, hair under the arms (axillary hair), in the pubic area, and on the trunk may be unusually sparse or absent. According to reports in the medical literature, the hair loss seen in those with Werner Syndrome may occur secondary to impaired functioning of the ovaries in females or the testes in males (hypogonadism), an endocrine condition associated with deficient growth and sexual development. Both males and females with Werner Syndrome may be affected by hypogonadism. As a result, affected males usually have an unusually small penis and small testes. Some females with the disorder may fail to develop secondary sexual characteristics (e.g., appearance of axillary and pubic hair, breast development, menstruation) and have poorly developed genitals. In other affected females, menstruation may be spare and irregular. Due to hypogonadism, most of those with the disorder may be infertile. However, there have been reports in the literature confirming that some affected males and females have reproduced.
Individuals with the disorder develop an abnormally high-pitched voice. In other cases, the voice may be squeaky or unusually hoarse.
By approximately 25 years of age, individuals with Werner Syndrome also develop progressive skin changes, particularly affecting the facial area, the upper arms and hands, and the lower legs and feet (distal extremities).
Causes
Werner Syndrome is transmitted as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
The parents of some individuals with Werner Syndrome have been closely related by blood (consanguineous). In these cases, if both parents carry the same disease gene, there is a higher-than-normal risk that their children may inherit the two disease genes necessary for the development of the disease.
Researchers have determined that Werner Syndrome is caused by abnormal changes (mutations) of a gene (known as the WRN gene) located on the short arm of chromosome 8 (8p12-11.2).* More than 80 different mutations of the WRN gene have been identified in individuals with the disorder.
 
Affected Populations
Werner Syndrome is a rare disorder that affects males and females in equal numbers. Since the disorder was originally described in the medical literature in 1904 (O. Werner), more than 500 cases have been reported. The disorder’s frequency has been estimated at one to 20 per one million individuals in the United States. Although certain associated findings are present beginning during childhood, puberty, and young adulthood, the disorder is most frequently recognized in the third or fourth decades of life.
Related Disorders
Symptoms of the following disorders can be similar to those of Werner Syndrome. Comparisons may be useful for a differential diagnosis:
Hutchinson-Gilford Progeria Syndrome is a very rare disorder of childhood characterized by premature aging, short stature, and characteristic facial features. The primary symptoms of this disorder are those associated with the aging process. Children with this disease age very rapidly and suffer with disorders of the aged while they are young. At approximately 10 years of age, most children with Hutchinson-Gilford Progeria Syndrome attain the height of an average 3 year old child. Arthritis often effects bone joints during childhood and adolescence. (For more information on this disorder, choose “Hutchinson-Gilford Progeria” as your search term in the Rare Disease Database.)
 

Diagnosis
In some cases, Werner Syndrome may be recognized clinically as early as approximately age 15, based upon a thorough clinical evaluation, characteristic physical findings (e.g., absence of growth spurt at puberty, short stature, low weight), and a careful patient and family history. However, the disorder often may not be recognized or confirmed until the third or fourth decades of life, once certain distinctive symptoms and findings are noted
Diagnostic testing may include monitoring of blood sugar levels to ensure prompt detection of diabetes mellitus, bone scans and blood tests for osteoporosis, and/or other studies. In addition, thorough cardiac evaluations and ongoing monitoring may also be performed (e.g., clinical examinations, X-ray studies, specialized cardiac tests) to assess associated cardiovascular abnormalities and determine appropriate disease management. Individuals with Werner Syndrome should also be regularly monitored as necessary to ensure the prompt detection and appropriate treatment of certain malignancies or benign tumors that may occur in association with the disorder (e.g., osteosarcoma, meningioma).

Treatment
The treatment of Werner Syndrome is directed toward the specific symptoms that are apparent in each individual. Disorder management may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected individual’s treatment. Such specialists may include internists; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and other related tissues (orthopedists); physicians who diagnose and treat abnormalities of the heart and its major blood vessels; eye specialists (ophthalmologists); physicians who diagnose and treat disorders of the endocrine system (endocrinologists); and/or other health care professionals. Specific therapies for individuals with Werner Syndrome are symptomatic and supportive. According to reports in the medical literature, diabetes mellitus is typically mild and may often be managed with dietary changes and appropriate medications by mouth to decrease elevated sugar (glucose) levels in the blood (oral hypoglycemic medications).
 
 
 
 







bibliography:
Junko Oshima, Ph.D,George M. Martin, M.D.. (2015). Werner Syndrome. 26/11/15, de NORD Sitio web: https://rarediseases.org/rare-diseases/werner-syndrome
TEXTBOOKS
Emery and Rimoin’s Principles and Practice of Medical Genetics, 6th Ed: David L. Rimoin, Reed E. Pyeritz and Bruce Korf, Editors; Elsevier B.V., 2013, Pages 1-19.

Cecil Textbook of Medicine, 24th Ed.: Lee Goldman, Editor; W.B. Saunders Co., 2012. Pp.1340-1346.
Smith’s Recognizable Patterns of Human Malformation, 7th Ed.; Kenneth Lyons Jones, Marilyn Crandall Jones and Miguel Del Campo, Editors; W. B. Saunders Co., 2013. Pp. 188-201.
Syndromes of the Head and Neck, 5th Ed.: Raoul Hennekam, Judith Allanson, Ian Krantz, Editors; Oxford University Press, 2010. Pp. 586-590.


 

 

 

 

 


No hay comentarios.:

Publicar un comentario