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Fragile X Syndrome
Wednesday, 02 July 2003
Sunday, 30 October 2005
Martin-Bell syndrome, Marker X syndrome, FRAXA, X-linked mental retardation

What

Fragile X syndrome is a genetic disorder and the leading cause of inherited mental retardation. Children with this syndrome often have significant delays in learning, autistic-like behavior, hyperactivity, and a distinctive physical appearance. The term “fragile X” comes from the finding that the X chromosomes of affected individuals have a fragile site that causes the chromosome to break under certain test conditions.

Who

Fragile X syndrome is found in all racial and ethnic groups. This disorder is present from birth, but it is often not diagnosed until later in childhood or adolescence. It is inherited in an X-linked manner, meaning that the gene that causes this disorder is located on the X chromosome. The X and Y chromosomes are the chromosomes that determine the sex of a baby. Males have one X and one Y chromosome and females have two X chromosomes. Affected males inherit the affected X chromosome from their mother and their Y chromosome from their father. Females inherit an X chromosome from each of their parents. Because females have two X chromosomes they generally have no or much milder symptoms.

Signs and Symptoms

The presentation of this disorder can vary a great deal depending on the gender of the child as well as the severity of the genetic change. In early childhood, delays in development are often observed with speech and language being particularly affected. Parents often notice characteristics of attention deficit hyperactivity disorder and autistic behaviors, such as hand flapping, hand biting, and poor eye contact. Mental retardation may be mild to severe. Physical findings in early childhood are generally mild, and may include macrocephaly (large head) and frontal bossing (prominent forehead), and some exhibit hypermobility (excessive joint mobility). Other associated conditions include strabismus (unequal eye gaze), mitral valve prolapse (one of the heart valves does not close properly), and pes planus (flat feet). After puberty, some other physical findings become more noticeable, such as an elongated face, prominent jaw, large ears, pectus excavatum (chest wall over the breastbone appears sunken), scoliosis (inappropriate curvature of the spine), and macroorchidism (large testes) in males. Thirty percent of carrier males develop fragile X-associated tremor/ataxia syndrome, (FXTAS), after the age of 50. Symptoms include intention tremor, Parkinson’s-like features, and dementia. Premature ovarian failure (significantly early menopause) has been seen in 20 percent of carrier females, and is often the only abnormal finding in these women.

Possible Causes

The gene causing fragile X, FMR-1, is located on the X chromosome at the so-called “fragile” site that gives the syndrome its name. The protein it produces is believed to play a role in brain development. The FMR-1 gene was found to contain repeats of a particular 3-base CGG sequence. When the length of this repeat becomes too long it causes Fragile X syndrome.

Diagnosis

Fragile X syndrome is usually first suspected in children with mental retardation, developmental delay, or autism, especially if they have the associated physical or behavioral findings of fragile X, or a family history of fragile X or undiagnosed mental retardation. The diagnosis is then confirmed by specialized genetic testing.

Treatment

There is no specific treatment or cure for fragile X syndrome, but it is highly recommended for children to participate in global interventional programs to assist with learning disabilities and language-communication skills, such as sign language. Early detection allows for the appropriate behavioral, social and cognitive programs to be initiated as early as the preschool years. They will need individual education plans devised for their schooling. Children with fragile X syndrome are often referred to psychiatrists or behavioral specialists, and some may be prescribed medications to help control ADHD and autistic behaviors. Geneticists should be involved in counseling the patient’s family regarding future offspring. Referrals to other subspecialists will be made if needed (i.e. cardiologist for mitral valve prolapse, orthopedist for severe scoliosis).

Prognosis

The ability of individuals affected by fragile X to function independently throughout life is highly variable since the degree of delay experienced by these children ranges from mild to severe. With appropriate interventional programs, children with fragile X can achieve above the level that would have been predicted based on measured IQ alone. For this reason, early diagnosis is important so that assistance may be started sooner rather than later. In adulthood, these individuals may require some degree of assisted living, but life expectancy is no different from the normal population.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Carolina Fragile X Project
Focuses on increasing public awareness and understanding of fragile X syndrome, as well as different types of intervention available to affected individuals and their families.

Conquer Fragile X Foundation
Foundation that offers grants for research, also lists open studies for interested families. Accepts monetary donations and is active in lobbying for political initiatives to expand research opportunities.

FRAXA – Fragile X Research Foundation
Another foundation focused on promoting research, it also provides general information about the syndrome and offers publications, links, and contacts. They also accept financial donations and tissue donations for research.

The National Fragile X Foundation
An exceptionally thorough and comprehensive site, and thus a great starting point for parents in search of anything and everything. It includes a unique section on life-planning, which discusses financial planning, employment and community living.

NICHD: Families and Fragile X Syndrome
A nice publication for families produced by the National Institute of Child Health & Human Development, available for free at this website.

Google Search for Fragile X Syndrome

References and Sources

American College of Medical Genetics (1994). Fragile X syndrome: diagnostic and carrier testing. http://www.acmg.net/resources/policies/pol-014.asp Jewell J (2005). eMedicine: Fragile X syndrome. http://www.emedicine.com/PED/topic800.htm Wattendorf DJ and Muenke M (2005). Diagnosis and management of fragile X syndrome. Am Fam Physician 72(1): 111-113.