Fragile X Syndrome

Don't be fooled by its rather delicate name. Fragile X Syndrome (FXS) is a powerful disorder that crosses all racial and ethnic lines, according to the March of Dimes (MOD). The National Fragile X Foundation, (NFXF) calls it the most common form of inherited mental retardation. (Read about "Genetics") (Read about "Birth Defects") While the exact number of people who have FXS is unknown, the Centers for Disease Control and Prevention (CDC) estimate that about one in 4000 males and one in 6000 to 8000 females has the disorder. FXS was first investigated in the 1940's; but the mutated gene that causes fragile X wasn't identified until 1991, according to NFXF. Fragile X gets its name from the microscopic appearance of the part of the mutated X chromosome. According to MOD, the section of chromosome looks fragile, as if hanging by a thread.

Cause of FXS

Fragile X is a genetic disorder. That means it is passed down in families. (Read about "Family Health History") In 1991, a researcher discovered that FXS is caused by a mutation in a gene. That gene, called FMR-1 is located on the X chromosome. We all have 23 pairs of chromosomes and one pair is referred to as the sex chromosomes. They are called X or Y. Women have two X chromosomes while men have one X and one Y. If a female inherits one X chromosome with the mutated FMR-1 gene, she essentially has a spare X. That's why, according to MOD, females tend to have fewer symptoms of fragile X syndrome than males.

The FMR-1 gene can show up in four different ways, according to March of Dimes. It all depends on a genetic stutter called a repeat. When a small section of genetic material inside the gene is repeated too many times, it can mean the difference between a normal life and one with fragile X syndrome. MOD categorizes the number of repeats in the following ways:

• normal - 45 or less
• gray zone - 45-55 - repeats can grow with each generation potentially putting grandchildren at risk
• pre-mutation - 55-200 - both men and women can be carriers (however, in order for a child to have full-blown FXS, the mother must be a carrier)
• full mutation - 200 or more - causes fragile X

According to CDC, the gene is turned off once there are 200 or more repeats. As a result, a certain protein isn't produced. FXS is the result of the lack of that specific protein.

Men can only pass on a problem to their daughters since they do not pass their own X chromosome to their sons. Women can pass on the problem to both sons and daughters.

Symptoms of FXS

Children with full-blown FXS are usually diagnosed between 3 and 5 years of age, according to CDC. MOD says symptoms can range from mild to severe, and may include some of the following:

• a degree of mental retardation or learning disabilities
• autistic-like behavior; hand flapping and hand biting (Read about "Autism Spectrum Disorders")
• speech problems
• delays in sitting, walking and talking (Read about "Child Development")
• anxiety and mood issues (Read about "Anxiety")
• problems paying attention
• sensitivity to light, sounds, touch and textures
• physical features such as a long face, large ears, flat feet and flexible fingers
• males tend to develop enlarged testicles post puberty

MOD says that most children with FXS don't have serious medical problems and generally live just as long as any healthy adult, but a small percentage could develop the following:

• heart murmur (Read about "The Heart & Its Valves")
• seizures (Read about "Seizures")
• chronic ear infections (Read about "Otitis Media")

People who don't have the full FXS mutation may also suffer from unusual symptoms. CDC says that those with a pre-mutation may suffer from nervous system and behavioral disorders as well as infertility. CDC lists the following details of such problems:

• premature ovarian failure - women stop having menstrual cycles before 40 years of age (Read about "The Ovaries" "Menopause")
• learning and behavioral problems - mood disorders, learning disabilities and some autism spectrum disorders (Read about "Autism Spectrum Disorders")
• fragile X associated tremor/ataxia syndrome - tremors, problems with walking and balance, memory loss; men are more affected than women and usually develop symptoms when they are over 50.

Testing

FXS can be diagnosed from a person's DNA through a blood sample. (Read about "Laboratory Testing") CDC says a physician or genetic counselor can order the test. The DNA test will reveal if there is any abnormality in the FMR-1 gene.

If your healthcare provider recommends testing, MOD says one or all of the following may be the reason:

• a child has mental retardation, developmental delays or autism
• there is a family history of FXS or mental retardation without a known cause
• the child has physical and/or behavioral characteristics of FXS
• a woman with a family history of FXS is planning a pregnancy
• a man or woman suffers with a tremor, and may have a family history of FXS

MOD says prenatal tests (Read about "Pregnancy Testing") can also determine whether the baby of a carrier mother will inherit the full or pre-mutation. MOD notes that some people with the full mutation, particularly females, will not always have mental retardation.

Treatment

There is no cure for FXS, but according to MOD, treatment plans can be put into place to help those affected reach their maximum potential. (Read about "Rehabilitation") MOD says members of a treatment team may include:

• language/speech therapists
• physical/occupational therapists
• special educators
• psychologists
• pediatricians

According to MOD, some medications may help improve behavioral symptoms, which in turn can help with learning. Commonly used medications may include:

• antidepressants
• stimulants
• antiseizure drugs

Research

Researchers are investigating how the loss of protein made by the FMR-1 gene interferes with brain activity. (Read about "The Brain") They are also studying how the gene mutation contributes to autistic like behaviors. The goal is to develop effective diagnosis and treatments for both fragile X syndrome, and autism.