Fragile X Syndrome

What is Fragile X? Fragile X, also known as Martin-Bell syndrome, is an X-linked genetic disorder. It is the most common inherited cause of mental impairment and autism. Fragile X is carried by 1 in 260 women and 1 in 800 men. It affects 1 in 4,000 males and 1 in 6,000 females.

What causes Fragile X? Fragile X is inherited in an unusual pattern. The mutation is the amplification if the CGG triplet repeat sequence on the Fragile X gene. In other words, the triplet sequence is repeated too many times. When this sequence is repeated too many times, the gene is unable to make enough of the protein FMRP.

A normal gene will have between 5 and 45 repeats A normal gene will have between 5 and 45 repeats. A gene with premutation will have between 50 and 200 repeats. A gene with the full mutation will have more than 200 repeats. Depending on how many times the triplet code is repeated, different amounts of FMRP will be produced. Different amounts cause different severity levels. The less FMRP you produce, the more severe. A molecular analysis of a blood sample can be used to determine if you are a carrier or contain the full Fragile X mutation.

How is Fragile X inherited? Since the gene is carried on the X chromosome, both males and females can pass on the gene. A father can only pass the gene on to his daughters, and even if he has the full mutation the daughters will only receive the premutation gene. A mother can pass the carrier and full mutation gene to sons and daughters.

What does Fragile X look like? A full mutation chromosome will look like the top picture. In the full mutation, all the way at the bottom, the promoter region is 12 times longer than the normal promoter region.

What are the symptoms/effects? Many people with Fragile X have impaired intellectual functioning, which affects their ability to think, reason, and learn. Some physical signs of Fragile X are long face or jaw, more noticeable ears, and flexible joints. Many children with Fragile X, especially boys, feel a great deal of social anxiety. They also tend to be easily upset. Language difficulties can range from mild to severe. Males with Fragile X may stutter or repeat themselves many times.

Is there treatment? Currently there is no single treatment for Fragile X. Individualized Education Plans are designed and include specific goals depending on needs and capabilities. Speech-language therapists, occupational therapists, and behavioral and physical therapists work to help individuals with Fragile X and their families deal with the symptoms.

Current Research An area of focus for Fragile X research is the inheritance patterns of the chromosomal mutation. Research has found the pathway which is defective in Fragile X and drugs are now being developed to target this pathway.

Other Information Nearly 20 percent of Fragile X males are silent carriers, who are unaffected by the syndrome but can pass the Fragile X chromosome to their female offspring. About one-third of female Fragile X carriers, who would be expected to not show symptoms, exhibit some symptoms of the disorder. 1 in 260 women have the pre-mutation, but many will never know. Fragile X is not deadly and will not shorten lifespan. There is a support group called Fragile X Syndrome Support Group on Daily Strength, on online help site.

A Fragile X Story My son, Ridge Damon, is fifteen years old. He was born with a condition known as Fragile-X Syndrome. He has disabilities that hamper his ability to interact with other people, plus he has some accompanying physical features that are hallmarks of the syndrome. For example, Ridge is extremely shy when meeting new people.  He always has been; it is very hard for him to make friends.  He's also nervous, agitated, and has some nervous habits (hand flapping, head shaking, limited eye contact with others, and has problems with remembering things when introduced to new situations). Ridge is in special education classes; they are working with him to try to improve his behavior and socialization skills.  We don't know if it is really helping; however we are more than willing to do anything for our son, to make his life a little bit better, not to mention, easier. Ridge has some unusual features that make him stand out from the crowd:  an elongated face.  Mental disabilities that make him seem much younger than what he truly is (mentally, he functions at about a five-to-six year old child).  Large, protruding ears.  Flat feet.  Low muscle tone.  Smooth skin.  Atypical socialization skills (shyness, limited eye contact, memory problems, etc.).

Sometimes Ridge will get frustrated when learning new things that he will go into a rage.  It is always very stressful for us (and for him) when this happens.  We try everything under our power to keep the routine familiar with him; we do try to introduce change; we just do it very slowly and over time.  We don't rush headlong into things; it would only lead to disaster. One time, Ridge got so angry he trashed the house.  Took us three days to clean up the mess he made.  He has a volatile temper; it is not pleasant! Besides the anger issues, Ridge also bites himself (hands mostly), or he rocks his body until he calms down.  Ridge is the only one out of our children who has this syndrome.  Our other three children (daughters) are all unaffected, although we do have a niece who has this (fragile-X is rarer in girls than in boys; many more males are affected).  (She's eight.)  Before our son had been born with this disorder, we'd never heard of fragile-X.  What we learned was truly eye-opening. Ridge will always need help with social skills, but with therapies or meds to help his behaviors, he should do fine.  He will be able to hold a job (in a sheltered workshop environment), and he will learn to socialize with others in time.  We just have to be patient is all.

Pictures

Bibliography Families and Fragile X Syndrome. [Rockville, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health [National Institute of Child Health and Human Development, 2003. Print. Fragile X Syndrome. Web. 21 Jan. 2011. <http://fragilexsyndrome.blogspot.com/>. "Molecular Analysis of Fragile X Syndrome | Current Protocols." Current Protocols | The Fine Art of Experimentation. Web. 21 Jan. 2011. <http://www.currentprotocols.com/protocol/hg0905>.  On the Verge of Breakthrough Treatment. Fraxa Research Foundation, 2007. Print. What Is Fragile X. Walnut Creek: National Fragile X Foundation, 2009. Print.