FXS Carrier Testing
What is Fragile X Syndrome?
Fragile X Syndrome is one of the most common genetic mental retardation diseases. The name derives from the fact that the patient’s x chromosome appears fragile at the end. Second only to Down Syndrome (average IQ 50), Fragile X Syndrome is the second major cause of mental retardation (average IQ 40).
95% of Down Syndrome is not caused by genetic disorders. However, Fragile X Syndrome is a sex-linked genetic disease. Besides mental retardation, the patient also has physical phenotypes, including a large forehead, protruding ears, prominent jaws, etc.
List of the Symptoms of Fragile X Syndrome
| Category | General Symptoms |
|
Physical Characteristics |
Not prominent during infantry, but the physical characteristics are more and more apparent when the patients grow older, such as a narrow face, a large head, a wide forehead, large ears, flat feet, etc. Male patients would have huge testicles during puberty. |
|
Mental and Learning Retardation |
Many patients have mental problems, with the average IQ of 40. Mild problems include difficulty in mathematics while severe cases would have mental retardation, difficulty in thinking, inference, and learning. |
|
Behavioral, Social, and Emotional Disorders |
Most patients would have behavioral changes. They might easily feel fear and anxiety in a new environment and be unable to contact with others. Males in particular might have difficulty concentrating on one thing or might be violent while females might be extremely shy. |
|
Language Problems |
It is more common for male patients to have language problems, such as inability to talk clearly and inability to understand social languages such as the tones or body languages. Some patients have language delay but most of them would eventually be able to speak. |
|
Dysfunctions |
Many patients would be affected by certain dysfunctions. For example, they might be affected by strong lights, noises, or what they wear. |
Reference: NICHD; the list is organized by GGA.
What causes Fragile X Syndrome?
Everyone has FMR1, but under normal circumstances, FMR1 will be stably passed down to the next generation. Fragile X Syndrome is caused by the genetic mutation of FMR1 and abnormal trinucleotide repeat, resulting in abnormal methylation and inability to produce FMRP for the generation of FMR1. It would affect brain growth and cause mental retardation.
When CGG of FMR1 is lower than 54, there would not be any clinical symptoms and the next generation does not have the risks of having the disease. However if CGG is between 55-200, namely “pre-mutation,” the person would be the carrier of the disease. Most of the female carriers do not have clinical symptoms or only have mild symptoms, but it is possible for them to pass down the mutated genes to their children, or turn into full-mutation when the number of CGG repeat increases when it is passed down to the children. When the CGG is larger than 200, namely “full-mutation,” the person is a patient of the disease.
| CGG | FMR1 | Clinical Significance |
| <45 | Normal | No clinical symptoms |
| 45-54 | Medium | |
| 55-200 | Pre-Mutation | Carriers of Fragile X Syndrome |
| >200 | Full-Mutation | Patients of Fragile X Syndrome |
Male Carrier Rate up to about 1/800
Female Carrier Rate up to about 1/260
If the female has FMR1 genetic mutation, 50% of possibility it would be passed down to the next generation.
Specimen
Adult: 3-5 c.c. blood
Fetus: 15 c.c. amniotic fluid
Examinations for Adults:
To better understand the condition.
Prenatal Examinations:
At early trimester, the mother can take FMR1 genetic examination to rule out the possibility for having a fetus with the disease.During 16-20 weeks of pregnancy, the mother can take amniocentesis as well as FMR1 genetic testing to make sure whether the fetus is inherited with abnormal genes with Fragile X Syndrome.
Applicability
Fragile X Syndrome Screening can detect whether the examinees are carriers and understand the risks of the next generation having Fragile X Syndrome.
- Those with a family history of Fragile X Syndrome
- Those with a family history of unknown mental retardation and autism
- Those with a family history of unknown ataxia and delirium.
- Those whose female family members have early menopause.
- Those worrying about being carriers.
