Fragile X Syndrome
What is Fragile X Syndrome?
JScreen now tests for the genetic condition fragile X syndrome on women as part of the Ashkenazi Jewish Panel and the Expanded Panel. Fragile X syndrome causes mental retardation and behavior problems and affects males more significantly than females.
Fragile X syndrome is inherited in a different way than the other genetic conditions on JScreen’s panels, and, unlike the other conditions, carriers could develop health problems later in life.
Fragile X syndrome is a condition that causes a spectrum of developmental and behavioral problems, which tend to be more severe in males. It is the most common form of inherited intellectual disability. As infants, children with fragile X syndrome may display poor muscle tone, gastric reflux, and frequent ear infections. Their motor and mental milestones, as well as their speech, tend to be delayed.
Children with fragile X syndrome often have behavioral problems such as anxiety, hyperactivity, handflapping, biting, and temper tantrums. Roughly 15% of males and 5% of females with fragile X will experience seizures. While some experience heart murmurs from a condition called mitral valve prolapse, it is usually harmless and may not require treatment.
Fragile X syndrome typically causes moderate intellectual disability in males, although the severity of intellectual impairment varies from person to person. A small number of males do not have intellectual disability, defined as an IQ below 70. About one-third of males with fragile X syndrome have autism or autism-like behavior. Males with fragile X syndrome often share characteristic physical features such as a long, narrow face with a prominent jaw and forehead, a large head, flexible joints, and large ears. These symptoms tend to be milder or absent in females with the condition. After puberty, males with fragile X syndrome typically have enlarged testicles.
In females, who often have milder symptoms, behavioral problems may appear as depression, shyness, and avoidance of social situations. Some people with the condition have attention deficit disorder, with an inability to sustain focused attention on a specific task. About a third of women with fragile X syndrome have no cognitive impairment, while the remainder have some degree of cognitive, behavioral, or social difficulties. Some females with fragile X syndrome have mild intellectual disability.
Inheritance
Fragile X is inherited differently than the other diseases on JScreen’s panel.
In fragile X syndrome, the gene associated with the disease is located on the X chromosome. The X and Y chromosomes determine gender. Women have two X chromosomes (XX) while men have one X chromosome and one Y chromosome (XY). Girls receive one X chromosome from their mother and one from their father. Boys receive one X chromosome from their mother and a Y chromosome from their father.
Fragile X syndrome is among a group of diseases called “trinucleotide repeat disorders.” These conditions are caused by a sequence of DNA that is repeated over and over in the same gene. While everyone has these repeats, it is the number of repeats which determines whether or not a person has the disease or can pass it on to future generations.
Fragile X syndrome is caused by a mutation in the FMR1 gene. This gene contains a segment of DNA called the “CGG repeat,” in which a particular section of DNA is repeated a certain number of times in a row. By counting the number of CGG repeats that each parent has, we can determine the likelihood that his or her child will have fragile X syndrome.
FMR1 CGG Repeat Size
Category
Risk for an Affected Child
5-44 repeats
Normal
Very unlikely to have a child with fragile X
45-54 repeats
Intermediate
Low risk to have a child with fragile X
55-200 repeats
Premutation
Each child has a 50% risk to inherit his/her mother’s premutation. If the premutation increases to >200 repeats, the child will be affected.
>200 repeat
Full mutation
Individuals with >200 repeats are considered affected.
How Common is Fragile X Syndrome?
It is estimated that 1 in 4,000 males and 1 in 8,000 females are affected by Fragile X Syndrome.
Based on a review of the literature and Counsyl’s internal data, approximately 1 in 225 women carries a premutation and 1 in 45 women carries an intermediate allele.
How is Fragile X Syndrome Treated?
There is no cure for Fragile X Syndrome; however, children with the condition can be treated and supported in many ways. They may benefit from educational support like early developmental intervention, special education classes in school, speech therapy, occupational therapy, and behavioral therapies. A physician may also prescribe medication for their behavioral issues such as aggression, anxiety, or hyperactivity. A small number of these children experience seizures which can be controlled with medication. While some experience heart murmurs from a condition called mitral valve prolapse, it is usually harmless and may not require treatment.
What is the Prognosis for Someone with Fragile X Syndrome?
While many individuals with fragile X syndrome have learning and behavioral problems, they generally do not have major medical problems and can live a normal life span.
Premutation Carrier Health Risks
Testing for fragile X syndrome could reveal information that affects YOUR future health. Men and women with a premutation do not have fragile X syndrome, but may experience certain physical symptoms. While they are intellectually normal, they are thought to be more vulnerable to anxiety and depression. The key risks for carriers of a premutation are fragile X-associated tremor/ataxia syndrome (FXTAS) and premature ovarian failure (POF).
FXTAS: About 40% of men over the age of 50 with a fragile X premutation will develop FXTAS. (The percentage of women premutation carriers affected by FXTAS is unknown, but is thought to be lower.)
FXTAS causes an inability to coordinate muscle movements (ataxia) that worsens over time, tremors, memory loss, dementia, a loss of feeling and weakness in the lower legs, and some mental and behavioral changes. Often symptoms of FXTAS begin around age 60 with a tremor, followed several years later by ataxia.
POF: Some women with premutations experience premature ovarian failure (POF), in which their menstrual periods stop by age 40. Only 5 to 10% of women with POF will be able to have children. One study found that 21% of women with a premutation experienced POF, compared to 1% in the general population. Women with premutations larger than 80 CGG repeats were at lower risk for POF when compared to women with smaller premutations. Women with full mutations are not at increased risk for POF.
For more information about Fragile X Syndrome you can visit these sites:www.fraxa.org
www.FragileX.org
www.ncbi.nlm.nih.gov/books/NBK1384/
ghr.nlm.nih.gov/condition/fragile-x-syndrome
