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.

and please return the blog as it was before :((


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 

WEEK 4

ADOLESCENT PREGNANCY: EXPANSIVE PHENOMENON

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

WITHOUT WORK

Being women with a very young age, the vast majority of them is out of work when their children. In effect, the 11 thousand 527 cases of girls under 15 years who became mothers in the year 2011, only 812 had gainful employment; i.e., only 7% of them.

It is obvious that having a such a young age, their level of schooling is also very low; Thus, considering that up to 80% of these girls truncated his school career, it is expected that in the near future and in the long term, most go to confront extremely adverse conditions both in the workplace and in the academic.

In a similar case are adolescents who, at the time of the birth, had between 15 and 19 years of age, as 461 thousand cases of births recorded in 2011 in this age group, only 39 thousand 415 of these young people worked, i.e. just 8.35% of the total.

The data is noted, therefore having a short history of the school and almost zero work experience, the search for incorporation of these children and adolescents into the labour market is given in high risk conditions that shore, in thousands of cases, to accept conditions of informality, but in others of labour exploitation, and in extreme cases, to become victims of sexual exploitation or trafficking in persons.

Personal opinion

Unfortunately girls who became pregnant at his young age fail to finish his studies as primary and secondary basic although nowadays for any work already they ask for a high school and have come of age. many of these girls end up working in places where your payment is very little and too much time or many more do not work and only leave to their baby that's why we have to create awareness among them so that instead of becoming pregnant to achieve their goals and dreams and to see a better future, since everything has a time.

Andrea Martinéz Duran 

West Syndrome

The incidence of infantile spasms was between 0.25 and 0.4 per 1000 births. Children would be a little more affected than girls.
In 90% of cases, crises appear before one year of age, 10% before the third month. The maximum distribution is between the 4th and 7th month, more frequently in the 6th month. The later start (after 18 months), are nosological errors. A very early onset (before the third month) can be seen especially in the symptomatic forms.
In 9% of cases they were found a history of seizures and convulsions. It is strange (of 4 to 6%) the presentation of several cases of West syndrome in the same family. Transmission is autosomal recessive, rarely being linked to sex.

West syndrome is characterized by a symptom triad:
Infantile spasms that occur in salvos.
Impairment of psychomotor development.
A E.E.G. particularly intercritical: The hypsarrhythmia.
These three elements appear over several weeks in a child previously normal or already submitted crises or deficient neurological signs. In 85% of cases starts with spasms, sometimes with the arrest of psychomotor development. The layout may be missing hypsarrhythmic initially discovered or after the onset of spasms is well advanced. In typical cases, the syndrome set is completed in 4 to 6 weeks.

SEMIOLOGY OF THE CRISIS: The crisis in the West Syndrome have been called in several ways: flexion spasm, myoclonus Mass in flexion, Infantile Myoclonus, Lightning Seizure, Salaam Attack, Nodding Spasm or Blinking, Jerk of Infancy Epileptic, Blitz Krampf, Saalam Krampf, Nick Krampf and Propulsiv Petit Mal.
The clinical expression of spasms depends on the affected muscles and the duration of each spasm. The use of video methods has allowed a more detailed and rigorous analysis.

TYPICAL CRISIS. Much of the authors admitted that in most cases (68 to 80%) spasms occur in bending. They can be more or less extensive and affect the muscles of the neck, trunk and limbs; the child bends "as a razor to close": flexion of the head and trunk, upper limbs intertwine over the chest, lower limb triple flexion.

If the spasm is performed in extension (22.5% of cases), neck and trunk are extended and the members are placed in extension-abduction, separating crosshair. However, most often they are mixed-in flexion / extension-then pretending massive myoclonus.

ATYPICAL CRISIS. Often limited or frustrated in expression, risk being ignored or misunderstood: shake of the head, brief contraction of the abdominal muscles, lift your shoulders, simple adduction or adduction of the arms; more rarely spasm may be asymmetric (0.6%). Exceptionally crisis can be expressed by a akinesia and decreased reactivity (1%).

In general, a single child has several types of spasms.

Certain phenomena may accompany crises: ocular deviation (55%), respiratory distress (59.2%), abnormal heart rhythm. A cry or smile unmotivated conclude the crisis. Due to the short spasm, it is difficult to assess the level of consciousness; in the longer a temporary or atypical crises clouding supported.

If at the start of the condition spasms can be isolated, sporadic, preferably emergence or awakening during sleep, in the phase of state are characteristic saved (78.3% of cases). During a particular saved, the intensity and frequency increase progressively, to then decrease and disappear. They are favorable factors postprandial phase, a sudden noise or a contact.

PSYCHOMOTOR Regression: This is the second characteristic feature of the syndrome. Starts disease in approximately 15% of cases.

Its beginning is manifested by a modification of humor. In several days, the child falls into total indifference: loss of smile, reactions to sensory stimuli. Often the child is qualified deaf or blind, loss of facial expression and motor absolute immobility.

In the older child, selflessness extends to objects that are presented. This indifference, this lack of activity, sometimes give rise to stereotyped activities; more rarely, reactions of aggression or irritability are observed.

Then the impairment is confirmed, the child does not progress, it does not present any new acquisition. By contrast, activities that had lost at the start of his illness: he no longer feels not holding the head, he does not smile more ...

The loss of the most basic and widespread contacts sluggish own stigmas are an obvious regression if they occur in a child whose psychomotor development was already disturbing.

Diagnosis

The diagnosis is based on the triad of infantile spasms, impaired psychomotor development and EEG hypsarrhythmic.

In typical, complete forms, it is easy not done, because the clinical history and EEG rule out:

Misinterpretation of the parents, including doctors, spasm in flexion: flexion abdominal colic can simulate a child or an attempt to sit.

The Tic Sleep or Jactatio Capitis Night: lateral movements of the head, swinging, appearing in normal children during drowsiness or sleep.

The Spasmus Nutans, rhythmic oscillations of the head during the day, even in normal children.

The slow rhythmic swing of some deep backward (Tic Salaam).

Certain conditions must be differentiated West Syndrome:

Specific secondary generalized epilepsies can be expressed at the start by infantile spasms;

The Lennox-Gastaut syndrome, by the fact that the evolutionary continuation of some syndromes West, but its onset is later; there are others associated with those crises, like infantile spasms, where the EEG is different.

Certain conditions described recently seem more or less integrated within West syndrome. They are described at the end of this chapter.

Finally, Lombroso has described a benign myoclonic epilepsy of infancy. Crises are fully comparable to those of the West Syndrome but not altered mental state, EEG It is normal and crises disappear without sequelae before 2 years of age.

In my opinion it is vital that we as nurses know how to act in a case of West syndrome because it is a disorder uncommon but very traumatic for both the patient and the family because in this case it comes to young children besides all are sick, so we can understand their needs and meet them to provide better care to the patient.

Recovered  of http://www.apiceepilepsia.org/Sindrome-de-West-o-Espasmos-Infantiles on 23th november, 2015 at 18:35 by. Rebeca Guzman 2719140

Moya moya disease

Moyamoya disease (MS) is a vascular disease characterized by a progressive stenosis (until occlusion) of the terminal portion of both internal carotid arteries, which may include anterior cerebral artery (ACA) and medium (ACM) associated an abnormal vascular network called moyamoya vessels. It is a rare disease in children, so the aim of this publication is to put it in mind as a differential diagnosis in boxes origenvascular symptomatology, guiding the mind-directed study to your search. This becomes more important when you consider that is a progressive disease, which diagnosed early, can monitor your progress and avoid clinical deterioration that can be disabling, or even fatal consequences.

Takaku4 Susuki and in 1969 nominated this clinical entity, "smoke volcanoes" in Japanese, moyamoya, due to the appearance with angiographic images. Its etiology is still unknown, although epidemiological studies suggest genetic factors in its pathogenesis.

In children it is usually presented as transient ischemic attacks and strokes, with progression can be slow, with intermittent events, or fulminant with rapid neurological compromise. Diagnosis is based on clinical and radiological findings that show the characteristic internal carotid artery stenosis with abundant collateral vessels. The evolution without treatment is inevitably progression and clinical vascular compromise.

Cerebral revascularization surgery improves long-term prognosis, the various techniques described are intended to prevent ischemic damage greater increase collateral blood flow through the external carotid.

Below we describe our experience with two patients who were diagnosed with MS in Pediatric Critical Patient Unit of Clinica Santa Maria (UPCP-CSM) between January 1998 and December 2007. During this period have graduated 17 patients with stroke brain (AVE), a total of 5864 hospitalized patients, MS corresponding to 11% of stroke in patients between 15 days and 17 years, with an incidence of 0.2% per center per year.

Its etiology has not yet been clarified; There is growing evidence of the involvement of a genetic factor. It has been linked to several different genes located on chromosomes. D353050 reference to markers located in the 3p24.2-268 chromosome, D175939 chromosome 17q25, also in other parts of the same chromosome region contained in the 9-CM, D 175,785 to D1758369 is made, and on chromosome 6 in D6S44110. Polygenic inheritance autosomal dominant pathway low penetrancia11 is proposed. The family presentation, although it has been reported mainly in Japanese population, cases have also been reported in other parts of the world.12. The description of a G / C heterozygous genotype in position -418 in the promoter of tissue inhibitor of metalloproteinase 2 (TIMP2) could be a genetic factor predisposing to familial MS

Several studies of clinical, laboratory and pathological have tried to define its pathogenesis. It described an intimate thickened HERE samples of patients with moyamoya, techniques immune reaction suggestive of overexpression of factor-1 (alpha), inducing hypoxia and endoglinas in the intima of the ACM. Along with the aforementioned genetic factors, environmental factors also play a role, as suggested by Ulrich, who reports that 3.5% of children who had received radiotherapy for primary brain tumors, especially in the vicinity of the circle of Willis, developed MS in the follow-up, which was related more to those with type 1 neurofibromatosis and those receiving more than 5000 cGy of radiation. Other studies have been directed to seek soluble adhesion molecules in cerebrospinal fluid (CSF) of patients, suggesting an inflammatory process in the etiology of this enigmatic disease, that would be supported by the description of an MS by angiography in a 20- years, eight months after submitting a pneumococcal meningitis. It has also been associated with apoptosis, evidenced by the detection of activated caspase-3 (for technical immunoreaction) in the tunica media of the ACM with thinning of the vessel wall and the description of a high proportion of endothelial anticélulas serum antibody MS patients. On the other hand, publications that report the persistent trigeminal artery and the artery Bernasconi-Cassinari, both embryonic arteries, allowing suspect an early onset of the disease. 

In my personal opinion Moyamoya disease is a disorder that occurs in children, and causes various problems in the child's brain.

it is important that we know as nurses provide care to patients who suffer because it is very difficult to bring the symptoms for both parents and for the child.

Recovered of http://www.elenciclopedista.com.ar/enfermedad-de-moyamoya/ on 20th november, at 18:40 

By Rebeca Guzmàn

Genetic mutations: FRAGILE X SYNDROME

Genetic mutations: FRAGILE X SYNDROME

Concept

The fragile X syndrome (FXS) is the most common inherited genetic syndrome causing mental retardation and one of the best characterized forms of autism spectrum. It mainly affects men who have a characteristic phenotype and transmitted mainly by women. Its name is due to a narrowing of the distal end of chromosome X (Xq27.3) that appeared in the karyotype of affected individuals, and "fragile site" was called. In 1991, the gene responsible for this syndrome was identified, a fact which replaced the cytogenetic analysis as a diagnostic method.

Prevalence

The prevalence of FXS has been revised downward. Initial estimates of speaking of 1: 1250 affected males in the general population, has been passed to a prevalence of between 1: 4,000 and 1: 6,000. The figure for females is approximately half (1: 8000-1: 12,000). The prevalence of carriers in the population is about 1: 250 women, the relationship to the male carriers is 3: 1.

 

Genetic causes fragile x syndrome (fxs)

The genetic cause of FXS is a mutation or change in the normal sequence of DNA in the FMR1 gene, resulting in inactivation of the same and thus, lack of protein synthesis (FMRP) synthesizing.

The most common mutation involves elongation (expansion) of a small part of the sequence formed by repeating the nucleobases cytosine-guanine-guanine, which is called abbreviated CGG. This CGG triplet repeat is at the beginning of the gene, in an area that has no information for the protein it encodes, but rather had to do with his activity, in particular, that more or less copies of the FMRP protein is synthesized . This repetitive sequence typically contains between 6 and 55 CGG triplet repeats, the most frequent of 30 repetitions. But in Fragile X expansion in the number of CGG triplet repeats of this it occurs to be more than 200.

 Clinical feature:

The main clinical feature of FXS is mental retardation in affected males is moderate while in women it is slight. Other features that are usually present in most affected males are elongated face with prominent chin and broad forehead, large ears and detached, hypermobility (with increased mobility especially in small joints) and large testicles (macroorchidism) after puberty.

Other common physical findings are: large head (macrocephaly), abnormalities in the mouth, high palate and crowded teeth in the jaws, flat feet, hands with fingers flared at its distal end, heart murmur, strabismus (eye muscle hypotonic) , recurrent otitis, overweight or obesity, epilepsy and generalized hypotonic. In individuals with FXS clinical findings vary with age, in the case of joint laxity decreases with age, or the size of the testicles that usually normal until puberty.
in the first years of life, it delays in acquiring psychomotor functions, especially the language, which is subsequently manifests repetitive.
In the preschool may not be obvious physical traits that occur in later life. With age also become more evident ophthalmic, orthopedic, heart and skin problems. For women affected (full mutation) clinical findings are especially facial, but appear less frequently and are milder than in the case of men.
Recently it described two late onset subphenotypes related SXF. One appears especially in men with premutation (PM) between 50 and 60 years, is a multisystem neurological disorder with ataxia and intention tremor, why it was called Tremor-Ataxia Syndrome associated SXF (FXTAS, Fragile X-associated Tremor / Ataxia Syndrome).

Most frequent clinical manifestations:

Physical

• Long face with high forehead and prominent chin

• Large and protruding headphones Fields

• Joint hypermobility

• Large Testicles (macroorchidism) after puberty

• Squint

• Flat Feet

• Heart murmur (mitral valve prolapse)

• Thin skin

Intelligence and behavior

  • Intellectual Disability (mild to moderate)

• delayed onset of language

• Attention Deficit Hyperactivity Disorder

• Avoidance look

• Pseudoautista behavior.

Treatment

 The cause of the clinical manifestations of FXS is the lack of expression of the FMRP protein. At present, studies are underway for a possible molecular therapy to compensate somehow the lack of this protein. Treatment should be based on a multidisciplinary action, including diagnosis and early intervention newborn, drug treatment of the clinical manifestations, the psycho-pedagogical support, speech therapy and occupational therapy.
Gene therapy, acting on the genetic defect or deficiency of the protein FMRP, it would be a chance to improve or reverse some clinical manifestations of the syndrome. This is the future and that the different research teams are based.
There is no cure, but there are drugs that effectively, treat many of the symptoms described.

Bibliography:

William Glover, Feliciano Ramos .etal. (2006). FRAGILE X SYNDROME. Madrid, Spain: GIRMOGEN.
MP Ribate Molina, J Foot Juste, FJ Ramos Fuentes. (2010). Fragile X Syndrome. 19.11.15, Spanish Association of Pediatrics Website: http://www.aeped.es/sites/default/files/documentos/sindrome_de_x_fragil.pdf