Genetic mutations: Wolf-Hirschhorn syndrome

Wolf-Hirschhorn syndrome (4p16.3 deletion)

Wolf Hirschhorn syndrome or 4p- is a rare developmental disease characterized by multiple congenital anomalies and mental retardation. An incidence of 1 per estimated 50,000 newborns. It is characterized by a peculiar shaped face Greek helmet, microcephaly, cranial asymmetry, hypertelorism, bilateral coloboma, retrognathia, carp-shaped mouth, dysplastic and low-set ears, seizures with usually 9-10 months early start, congenital heart disease (which is present from birth): aortic coarctation, atrial and ventricular septal defect, incurvado penis, hypospadias, renal hypoplasia or absence in less than 10% of cases and mental retardation.

Physical signs and symptoms

·         Its main features are:

·         Typical childhood craniofacial features consisting of "short Greek warrior helmet appearance of the nose (the bridge of the nose continues on the wide front), microcephaly, high forehead with prominent glabella, ocular hypertelorism, epicanthal folds, highly arched eyebrows, filtrum , mush mouth, micrognathia and malformed ears with pits / tags.

·         All affected individuals have prenatal onset growth deficiency followed by postnatal growth retardation and underdevelopment with muscular hypotonia.

·         The developmental delay or intellectual disability is present to varying degrees in all.

·        Seizures occur between 50% and 100% of children with SWH.

·         Other findings include skeletal abnormalities (60% -70%), congenital heart defects (~ 50%), hearing loss (mostly drivers) (> 40%), urinary tract malformations (25%), and structural brain abnormalities (33%).

·         Low birth weight.

·         Muscle tone at birth.

·         Small head (microcephaly).

·         Skull with asymmetry.

·         Lip and cleft palate (cleft lip) in 50% of patients.

·         Distinctive face; Greek helmet shaped.

·         Jaw rearward.

·         Low-set ears.

·         A set of specific features of the eyes is presented.

·         Lack of tear duct.

 

 

 

 

 

 

 

 

 

 

 

 

Although it is difficult to determine the frequency of this syndrome in newborn infants, has been estimated at between 1 / 50,000 to 1 / 20,000 births, and has been observed in all ethnic groups, most of them in women than men in a ratio of two one.

Medical Complications

·         Seizures: can start early from 9-10 months.

·         Congenital heart diseases: coarctation of the aorta, atrial septal defect, ventricular septal defect.

·         Hypospadias: malformation in which the male urethral opening is not located at the tip of the penis but in its bottom. In 50% of patients.

·         Malformations in the kidneys: incomplete or faulty development or absence of a kidney (less than 10% of cases)

 

Causes

The Wolf-Hirschhorn syndrome is caused by partial deletion of the short arm of chromosome IV, in particular in the region WHSC1 and WHSC2.

About 87% of the cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosomal translocation. The severity of symptoms and the expressed phenotype vary depending on the amount of genetic material has been removed. The critical region for determining the phenotype is in 4p16.3 and often can be detected by genetic and fluorescence in situ hybridization tests. It should always be offered genetic counseling to affected families with Wolf-Hirschhorn syndrome.

 

Cytogenetic diagnosis

The clinical diagnosis is not certain, but a suspicion that requires confirmation with the definite diagnosis obtained from cytogenetic analysis and / or molecular. By high resolution chromosome study (500-850 bands) the deletion was detected only in 70% of cases with clinical diagnosis. This is because the loss of the end of the short arm of chromosome 4 may be very small, and techniques need whose resolution is higher. At present, the most used is the fluorescence in situ hybridization (FISH), with which the deletion is detected in up to 95% of patients with clinically suspected.

Treatment
So far there is no treatment for this disease. Treatment is directed to reduce medical complications that arise in each particular case. The prognosis is grave, about a third of patients die before two years of age, cardiological bronco pulmonary complications, and few cases have been described with 10-16 years than survival. Survivors have severe mental retardation and growth retardation prone to recurrent infections bronchopulmonary. It is associated with a deletion in the short arm of chromosome 4 (4p16.3). Most cases are 85-90% novo deletions.

Bibliography:

•  Alexandra M.D.; Isabella.; Maria Luisa M.F .; Maria D. S .; and Maria Luisa M.F .. (April 2010). Wolf-Hirschhorn syndrome. A S E R E M E C E M AC C, 20, 1-2.

•  Article: Wolf-Hirschhorn syndrome. May 28, 2011. Available at: "yasalud.com". Accessed: February 23, 2012.

•  Dr. Iacobini, Sandra.; Dra. Lotersztein, Vanessa and equipment. Medical News: "Rare diseases" or "orphan". Available in: "www.intramed.net". Cosnultado: February 23, 2012.

•  Aviña orge A. F .; Daniel A. Hernández A. Wolf-Hirschhorn Syndrome: distal microdeletion short arm of chromosome 4. 3 November 2007. Available at: "www.scielo.cl". Cosnultado: February 23, 2012.

WERNER SYNDROME

I share an important fact about why the name of Werner syndrome and clinical manifestations were analyzed spending time And the genes that are associated with Werner syndrome.

Werner Syndrome was first described by Dr. Otto Werner at the Kiel University in 1904 (Werner, 1904). In his thesis, Dr. Werner described scleroderma-like skin and cataracts in a sibship. Because this disorder shares some aspects of aging as described for two Japanese-American sisters, WS has been described as the "caricature of aging" (Epstein et al., 1966). 

Symptoms of some aging disorders, such as Hutchinson-Gilford progeria, may start to develop as early as infancy (Brown et al., 1985). In contrast, WS patients usually develop normally until they lack the pubertal growth spurt during adolescence, a symptom often recognized only retrospectively. Previous studies indicate that, although patients suffer a wide variety of age-related disorders, the chronology of symptoms appear to be similar between Caucasian and Japanese WS patients (Epstein et al., 1966; Goto et al., 1997). 

Individuals with the WRN null mutations prematurely develop an aged- appearance and age-related disorders including graying of the hair, hair loss, tight skin, cataracts, diabetes mellitus, hypogonadism, osteoporosis, atherosclerosis and cancers (Epstein et al., 1966; Martin et al., 1978; Tolesfbol and Cohen, 1984; Goto et al., 1997). The average age of clinical diagnosis of this syndrome is in the late thirties, and death usually occurs before the age of 55. The most common cause of death is cancer, followed by a vascular disease such as atherosclerosis (both myocardial and cerebrovascular). 


What genes are related to Werner syndrome?

Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA. This protein also assists in the process of copying (replicating) DNA in preparation for cell division. Mutations in the WRN gene often lead to the production of an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported to the cell's nucleus, where it normally interacts with DNA. Evidence also suggests that the altered protein is broken down more quickly in the cell than the normal Werner protein. Researchers do not fully understand how WRN mutations cause the signs and symptoms of Werner syndrome. Cells with an altered Werner protein may divide more slowly or stop dividing earlier than normal, causing growth problems. Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause the health problems associated with this condition.

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.

 

 

 

 

 

look companions found a brief explanation of the craniotomy to follow the link and see what the other side will serve them learn some anatomy.

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CLICK AQUI    ---> craneotomia

WEEK 7

LATIN AMERICA IS THE ONLY REGION WHERE INCREASED PREGNANCIES IN ADOLESCENTS

http://www.bbc.com/mundo/noticias/2013/10/131030_salud_embarazo_adolescente_onu_gtg

Pregnancy of young people under 18 years has not only not diminished in Latin America, but it has been an increase in recent years. This puts the region as the second with more child maternity, after Africa

The reason why every time there are more pregnancies in adolescents in the region is because - according to the Director for Latin America and the Caribbean of the UNFPA Marcela Suazo - poverty, gender inequality, discrimination, lack of access to services and social concept that we have of women and girls. The global study was done with the data collected from 54 countries from two sets of surveys conducted between 1990 and 1997 and 2008 and 2011 respectively. They show that in general terms there was a decrease in the percentage of women who had a birth before age 15. A trend that was not replicated in Latin America, where it is expected that these pregnancies continue to increase slightly until 2030.

"I think it is very important to recognize that there are multiple causes that can contribute to a teenage pregnancy, although there are four clearly defined," explains Suazo to BBC world. "Income level, the lack of access to education, the difference in access to services in rural areas regarding the urban and the relationship of pregnancy between afro-descendant indigenous and not afro-descendants". The report indicates that there are more pregnancies in teenage girls in the poorest percentile of the population. In addition, "many there is less chance of having a teen pregnancy if girls remain in school," said Suazo.

Opinion personal

We have discussed this subject throughout these weeks and we can observe that you cause more notable there is no communication with the girls this is could avoid from home as if we have a talk with the little of what sexual relations consequences of having them at an early age and more even if they suffer sexual abuse and we don't give them confidence so that they do not discuss it I think mothers and parents have a huge task and it is to report to their children about this.

andrea martinez duran 

WEEK 6

THE TRAGEDY OF GIRLS PREGNANT FOR VIOLATIONS IN LATIN AMERICA

http://www.bbc.com/mundo/noticias/2015/05/150512_america_latina_embarazos_ninas_violadas_vs

Belen was 11 years old when she became pregnant after being raped by her stepfather. His case caused a sensation in Chile a couple of years, since that country not allowed to abort despite a huge campaign that carried out civil society organizations concerned with the health of the child. Today another girl goes through the same experience to Bethlehem, and his case has again focused the interest of activists for human rights. Small lives in Paraguay and his name is kept in reserve to protect your identity. But it is known that it has just 10 years and carrying five months pregnant and a half.

Pregnancy seems to be the result of repeated abuse from her stepfather, who are currently detained, as well as her mother, accused of having unprotected. Amnesty International (AI) launched a campaign to demand that the Paraguayan authorities to be allowed to have an abortion, a claim which is supported by the High Commissioner for the United Nations human rights (UN) and other agencies. But despite the high profile that has acquired this case and the Bethlehem before, the truth is that their stories are not exceptional situations.

The Center for reproductive rights (CRR, by its acronym in English), an international organization dedicated to the defense of these rights, said to the BBC that there are hundreds of cases of girls pregnant after being raped in Latin America, but they tend not to be broadcast. It is a problem difficult to quantify. First, because many families do not report it since in general cases of abuse occur in the bosom of the family group. In these cases result rape babies tend to be declared "of unknown father", said to this medium who work closely with the pregnant minors. In addition, the majority of Governments has no statistics on that reality, explained to BBC World Monica Arango, Director for Latin America and the Caribbean of the CRR

Opinion personal

Unfortunately this happens most of the time since there are abusive people who take advantage of the trust that exists in the family environment and it is noteworthy that not only parents uncles cousins but also close to the family friends are cause both physical and psychological damage, and many of these times mothers know but for fear of being judged or same partners to stop them allow to keep this and follow up to the consequences of pregnancy in girls.

 Andrea Martinez Duran

WEEK 5

ADOLESCENT PREGNANCY: EXPANSIVE PHENOMENON

http://www.excelsior.com.mx/nacional/2013/05/07/897807#view-5

EARLY MORTALITY

The age factor is one of which represents increased quantity risks for health and life, both women who become pregnant to having less than 19 years, for their daughters and sons.

According to the INEGI data, maternal deaths of girls and adolescents represent, on average, 13% of the total of the revenue in the last two decades, i.e. between 1990 and the year 2010.

The data is worth to be highlighted, because the mortality in this age group has remained constant over the last 20 years, which means that the risks associated with pregnancy at a young age have failed to be reduced.

In this regard, perhaps to stand out is that in 2011 it was precisely record the percentage of maternal deaths in the adolescent age, because in that year these deaths accounted for 14% of the total number of deaths of women during or as a result of childbirth.

In absolute numbers, this means that of the 28 thousand 580 cases of maternal deaths has been in the country, three thousand 659 of them who were killed were girls and adolescents under 19 years.

That figure is higher than in maternal deaths in women aged 40 to 44 years; as including the accumulated over the past two decades is thousand 944 cases; This means that the risk of dying during or as a result of childbirth is practically doubled, when you have less than 19 years, that when you have exceeded the 40 years of age.

Personal opinion

We need to know that a girl's body is still not suitable to keep a baby in your body since they still do not have the same maturity that a mature woman, one of the causes of death is vaginal bleeding, bleeding and preeclampsia.

Andrea Martinez Duran