FRAGILE X
Definition: Fragile X Syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females. Fragile X Syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females.
Males and females with Fragile X Syndrome may have anxiety and hyperactive behavior such as fidgeting, excessive physical movements, or impulsive actions. They may also have attention deficit disorder, which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of males with Fragile X Syndrome also have Autism or autistic-like behavior that affects communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with Fragile X Syndrome.
Many males with Fragile X Syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, prominent jaw and forehead, unusually flexible fingers, and enlarged testicles (macroorchidism) after puberty.
Cause: Mutations in the FMR1 gene cause Fragile X Syndrome. The FMR1 gene provides instructions for making a protein called Fragile X mental retardation 1 protein, whose function is not fully understood. This protein likely plays a role in the development of synapses, which are specialized connections between nerve cells. Synapses are critical for relaying nerve impulses.
Nearly all cases of Fragile X Syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with Fragile X Syndrome, however, the CGG segment is repeated more than 200 times. The abnormally expanded CGG segment turns off (silences) the FMR1 gene, which prevents the gene from producing Fragile X mental retardation 1 protein. Loss or a shortage (deficiency) of this protein disrupts nervous system functions and leads to the signs and symptoms of Fragile X Syndrome.
Fragile X Syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.
In women, the FMR1 premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs. This means that women with the permutation have an increased risk of having a child with Fragile X Syndrome. By contrast, the permutation in men does not expand to more than 200 repeats as it is passed to the next generation. (Men pass the permutation only to their daughters. Their sons receive a Y chromosome, which does not include the FMR1 gene.)
Symptoms
Exams and Tests: The person will have a family history of Fragile X Syndrome (especially a male relative). There are very few outward signs of Fragile X Syndrome in babies. Babies may have a large head circumference. Measurement of oversized testes in males who have reached puberty may also suggest the diagnosis. An experienced geneticist may note subtle differences in facial characteristics. Mental retardation is the hallmark of this condition and, in females, this may be the only sign of the problem. A specific genetic test called polymerase chain reaction (PCR) is used to diagnose this disease. This test looks for an expanded mutation (called a triplet repeat) in the FMR1 gene.
In the past, a specific type of chromosome anaylsis was done. Such testing may still be available.
Treatment: There is no specific treatment for Fragile X Syndrome. Instead, effort is directed toward training and education so that affected children can function at as high a level as is possible. Because the condition is not rare, specific educational approaches have been developed and tested.
Support Groups
For more information on Fragile X
Definition: Fragile X Syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females. Fragile X Syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females.
Males and females with Fragile X Syndrome may have anxiety and hyperactive behavior such as fidgeting, excessive physical movements, or impulsive actions. They may also have attention deficit disorder, which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of males with Fragile X Syndrome also have Autism or autistic-like behavior that affects communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with Fragile X Syndrome.
Many males with Fragile X Syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, prominent jaw and forehead, unusually flexible fingers, and enlarged testicles (macroorchidism) after puberty.
Cause: Mutations in the FMR1 gene cause Fragile X Syndrome. The FMR1 gene provides instructions for making a protein called Fragile X mental retardation 1 protein, whose function is not fully understood. This protein likely plays a role in the development of synapses, which are specialized connections between nerve cells. Synapses are critical for relaying nerve impulses.
Nearly all cases of Fragile X Syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with Fragile X Syndrome, however, the CGG segment is repeated more than 200 times. The abnormally expanded CGG segment turns off (silences) the FMR1 gene, which prevents the gene from producing Fragile X mental retardation 1 protein. Loss or a shortage (deficiency) of this protein disrupts nervous system functions and leads to the signs and symptoms of Fragile X Syndrome.
Fragile X Syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.
In women, the FMR1 premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs. This means that women with the permutation have an increased risk of having a child with Fragile X Syndrome. By contrast, the permutation in men does not expand to more than 200 repeats as it is passed to the next generation. (Men pass the permutation only to their daughters. Their sons receive a Y chromosome, which does not include the FMR1 gene.)
Symptoms
- mental retardation
- large testicles (macro-orchidism) after the beginning of puberty
- large body size
- tendency to avoid eye contact
- hyperactive behavior
- large forehead or ears with a prominent jaw
Exams and Tests: The person will have a family history of Fragile X Syndrome (especially a male relative). There are very few outward signs of Fragile X Syndrome in babies. Babies may have a large head circumference. Measurement of oversized testes in males who have reached puberty may also suggest the diagnosis. An experienced geneticist may note subtle differences in facial characteristics. Mental retardation is the hallmark of this condition and, in females, this may be the only sign of the problem. A specific genetic test called polymerase chain reaction (PCR) is used to diagnose this disease. This test looks for an expanded mutation (called a triplet repeat) in the FMR1 gene.
In the past, a specific type of chromosome anaylsis was done. Such testing may still be available.
Treatment: There is no specific treatment for Fragile X Syndrome. Instead, effort is directed toward training and education so that affected children can function at as high a level as is possible. Because the condition is not rare, specific educational approaches have been developed and tested.
Support Groups
For more information on Fragile X
