Lucy Wacuka Mwaura

 Fragile X Syndrome Name Institution Fragile X Syndrome Summary Fragile X syndrome, previously called Martin- Bell, is considered the most common hereditary mental disability. The disease affects about 1 in every 6000 girls and 1 in every 4000 boys in the world (“What causes Fragile X,” 2017). People with the condition have a normal life although they may require care throughout their life. The disorder is caused by mutation of FMR1 gene that is found in the X chromosome. Mutation of this gene prevents manufacturing of protein leading to the different symptoms exhibited by people including intelligence problems, social and emotional problems, and speech and language problems. There are also some physical characteristics associated with the disorder including a long face, soft skin, large ears, and enlarged testicles. The disease can be diagnosed by carrying out prenatal tests during the mother’s pregnancy or after the child is born. The test is carried out on the DNA in an individual’s blood. The disorder does not have any known treatment, but a patient can receive speech and physical therapy. They can also take medication for mental disorders. However, there is ongoing research by scientists in the world for a cure to the disease. One of the most common types of hereditary developmental disability is Fragile X syndrome. It is considered the biggest cause of autism in the world. Fragile X affects 1 in every 6000 girls and 1 in every 4000 boys across the different ethnic groups and races in the world. The disease is caused by a hitch with FMR1 Gene. Usually, the gene is responsible for making a protein needed for development of the brain. However, the problem makes a person make either none or little of this protein, which results in Fragile X. Individuals who experience just small changes with these genes may not demonstrate any sign of the disease. However, people with great changes can show serious symptoms, which may include intelligence problem, emotional and social problems, and language and speech problems. Fragile X can be diagnosed using a blood test. The disease does not have a cure, but some of the symptoms can be treated with medicine and using physical, educational, or behavioral therapy. Early treatment is recommended. Individuals with Fragile X enjoy normal life expectancy, although most of them require care and support the whole of their life. Causes The cause of Fragile X is mutation of FMR1 Gene found in the X chromosome. A full mutation or a defect in this gene in people with Fragile X turns off the gene. The role of FMR1 is giving instructions for the production of FMRP protein, which helps in regulating production of proteins and in development of synapses. Mutation of the gene makes it defective, and it is unable to make the FMRP. Almost all the cases of the disease are due to mutation where a DNA segment, referred to as CGG triplet repeats, gets expanded inside the FMR1 gene. Usually, the DNA segment is repeated about 5 to 40 times. However, in people with Fragile X, the CGG segment gets repeated for over two hundred times. The unusually extended CGG segment silences the FMR1 gene, and this prevents it from producing FMRP. Shortage or loss of the protein disrupts the functions of nervous system and leads to the symptoms and signs of Fragile X. Females and males with between 55 to two 200 of CGG segment are considered having FMR1 gene premutation. Usually, such people are intellectually normal. However, in certain cases, they may have lower FMRP than normal. Consequently, they show slight version of the characteristics of Fragile X like prominent ears and may have emotional problems like depression and anxiety. A number of children having premutation show autistic-like behavior or learning disabilities. Premutation can also lead to increased risk of other disorders like fragile X-associated primary ovarian insufficiency or FXPOI and FXTAS or fragile X-associated tremor/ataxia syndrome. Inheritance Patterns Fragile X is inherited in a pattern that can be considered X-linked. The syndrome is considered as X-linked because the gene that causes it is found on one of the gender chromosome; X chromosome. The other one is the Y chromosome. Inheritance of the disorder is usually dominant if one of the copies of the altered gene in every cell is enough to cause fragile X. X-linked dominant implies that in women who possess 2 X chromosomes, a mutation in one copy of a gene in every cell is adequate to cause the syndrome. In males who posses one X chromosome, a mutation in one gene copy in every cell leads to the syndrome. In many cases, male exhibit more serious signs of the syndrome compared to their female counterparts. In female, the premutation of FMR1 gene can expand for over 200 CGG replicates in cells that grow into eggs. As a result, female with premutation have a higher risk of having a child with the syndrome. On the contrary, there is no expansion to more than 200 CGG replications in men as they are normally given to the subsequent generation. Premutation in men is only passed to their daughters, and sons get a Y chromosome that does not have FMR1 gene. Symptoms Fragile X syndrome affects more males than females. It is a genetic disorder that leads to a range of development related issues including intelligence problems that range from cognitive impairment and learning disabilities. People with the condition experienced delayed development of language and speech by the age of two years. The language and speech problem is especially common in boys. Patients may also exhibit emotional and social problems like shyness in females and aggression in males. A child with the disorder may be hyperactive and may also exhibit anxiety behavior including impulsive action and fidgeting. A third of people with the disorder may demonstrate features similar to those of autism spectrum disorders that affect social interaction and communication. Seizures may also occur in around 15 percent of male patients and 5% of females with the disorder. It may also lead to sensory integration issues including hypersensitivity to bright light and loud noises. There are physical features that characterize half of the females and most male with the disorder. The characteristics of the disorder in males include behavioral characteristics which include autism, ADD, ADH and autistic behaviors, hand-flapping and/ or biting, social anxiety, sensory disorders, reduced eye contact and increased aggression risks. Many of the male or boys with the disease show noteworthy intellectual disability. The disabilities in Fragile X may range from just mild learning disabilities to very serious intellectual disabilities. Boys with the disease have special characteristics including soft skin, long face, large ears, and macroorchidism or large testicles, especially in post-puberty stage. They may also have connective tissue troubles which include flat feet, ear infections, double-jointed finger, high arched palate and hyper-flexible joints. However, there is no single individual who can demonstrate all the features of Fragile X, and some characteristics like macroorchidism and long face become apparent after the puberty stage. Some males with the disease may demonstrate characteristics of being friendly, social, have excellent skills in imitation, strong long term or visual memory, are be helpful to other people are thoughtful and nice to people and demonstrate a good sense of humor. Females may also show some of the characteristics of males although they tend to have milder presentation of the disease, physical and behavioral features, and intellectual disability. About a third of the female patients demonstrate noteworthy intellectual disability. Other may show moderate learning disabilities, mental or emotional health issues, social and general anxiety. A little percentage of females with the full mutation of the gene that causes Fragile X will show no obvious signs of the syndrome- physical, behavioral or intellectual. They can only be identified after diagnosing another member of the family with the condition. Diagnosis A blood sample is used by healthcare providers in diagnosing Fragile X. The providers take a sample of blood which is taken to the lab to determine the form of FMR1 gene that an individual has. A test called prenatal testing may be done to women during pregnancy. Pregnant women with an FMR1 full mutation or premutation may pass the gene to their children. Testing during pregnancy helps healthcare providers in detecting mutated gene in the fetus. The information may help the providers and facilities in preparing for Fragile X and intervening early. Possible tests that can be used at this stage include amniocentesis where the health care provider uses a sample of the amniotic fluid. The fluid is then tested for availability of FMR1 mutation. The other test is chorionic villus sampling. In it, the healthcare provider sample of cells from the placenta is taken, and a test is carried out to check whether there is FMR1 mutation. Given that prenatal testing poses some risks to the fetus and mother, it is important for the family planning the test to discuss all the risks involved with a healthcare provider. The test is not common, and in most cases, many parents are not aware that they have the mutation. Thus, parents generally start to see symptoms in their children when they are toddlers or infants. On average, the age of diagnosis is 42 and 36 months for girls and boys respectively. In children, parents will see signs of delayed development; the symptoms may include delay in language and speech, emotional and social difficulties, and sensitivity to particular sensations. The children may also exhibit delay or problems with different motor skills like learning how to walk. In this case, healthcare providers may perform developmental screening in order to determine the type of delay that the child has. If they suspect that the child is suffering from Fragile X, they may refer him or her to a geneticist so that a genetic test can be done. The disorder can also be diagnosed using genetic testing where an individual’s DNA obtained from the blood is tested. The test can be ordered by a genetic counselor or a clinical geneticist. Testing is usually done to find whether there are changes in FMR1 gene that cause fragile X-associated diseases. Diagnosing Fragile X helps families by giving them explanation to behavior problems and intellectual disabilities in their children. Treatment Fragile X does not have a cure. Nonetheless, there are treatment services aimed at helping people with the syndrome to learn important skills. Such services include therapy to learn to walk, talk, and interact with other people. Additionally, medicine can be used for controlling some problems including behavioral ones. In order to come up with the best treatment strategy, people with Fragile X, health care providers, and parents need to work together and with other people involved in support and treatment including caregivers, teachers, therapists, coaches, and family members. Where the disorder was detected early in advance, services related to early intervention can be used to assist children from the time they are born to about 36 months in learning important skills. The services are important because they help in improving the development of the child. Children may be eligible for these services even if they have not been diagnosed with the condition. In the United States, the services are provided via a system for early intervention found in each state. Treatment of certain symptom of the syndrome like speech therapy done due to language delay may not need to wait for a diagnosis. Although early intervention is very important, treating people with the disorder regardless of their age is helpful. Given that the brain of a young child is still developing, early intervention may be appropriate because it gives these children the best chance of developing many skills. A child that starts intervention early has better chances of learning. Research Work Although there is still no cure for fragile X, some organizations like FRAXA are working towards finding a cure through accelerating the speed at which this research is conducted. Such organizations are also working towards eliminating the bottlenecks that hinder the process. One of the bottlenecks the organization is trying to eliminate is the fact that some years back, there was very little information about the effects as well as the causes of the diseases. The organization funded research in this area by recruiting neuroscientists, geneticists, and molecular biologists. FLAXA also hold booth every year that attracts about 30,000 scientists. Additionally, it holds a conference called Society for Neuroscience that is usually combined with Gordon Research Conferences and FLAXA Investigators Meeting. These conferences attract new talents that contribute immensely in the area of researching for a cure to Fragile X. Further, fragile X has become a very common topic today especially in Neuroscience with many scientists across the world are studying topics that are related to it. It has been possible to overcome other bottlenecks like intricacies in obtaining animal antibodies and models through grants such as FRAXA Mutant Mouse Resource that is at Baylor College of Medicine (Tranfaglia, 2016). The grant gives mice to scientists across the globe. Such grants have led to a sudden increase in translational research on the disease leading to numerous therapeutic strategies that are now being studied. References Tranfaglia, M. (2016). How close are we to a cure for Fragile X? Retrieved from https://www.fraxa.org/toward-a-cure/promising/ What causes Fragile X syndrome? (2017). Retrieved from https://www.fraxa.org/fragile-x-syndrome/cause/