Occurs in 1 in 4,000 males and 1 in 8,000 females
Escalante's syndrome (in Brazil and South America); fra(x) syndrome; FRAXA syndrome; FXS; Marker X syndrome; Martin Bell syndrome; X-linked mental retardation and macroorchisism
When a condition appears in a family, researchers begin creating a pedigree of the family tree marking the incidence of a disorder in the family. In 1943, Martin and Bell traced a pedigree of people with long, narrow faces and mental disability to the females of families. In 1969, Herbert Lubs, studying the genetic patterns, found an unusual “marker X chromosome” related to mental disability. Later, in 1970, another scientist, Frederick Hecht coined the term “fragile site.” The condition that these three scientists were researching is now called Fragile X syndrome.
Fragile X syndrome is an X-linked genetic condition, which results in a spectrum of intellectual and behavioral actions ranging from mild to severe. Because of the relationship to the X chromosome, males are mostly affected; however, if the female gets one gene from the father and one from the mother, she may also have fragile X syndrome.
In addition to learning disorders and cognitive disability, the person with FXS may have the following characteristics:
Facial appearance: Long face with large or protruding ears, protruding jaw, and high forehead. The characteristics may become more pronounced and abnormal appearing with age.
Behavior: The person displays extreme hyperactivity and attention disorders. They may display fidgeting, hand flapping, impulsivity, and problems focusing on tasks.
Communication: About one-third of the males have autistic-like behaviors that affect social interaction and communication.
Speech: Speech may appear cluttered and nervous.
Seizures: These occur in about 15% of males and 5% of females.
Body features: Fingers may be unusually flexible with double-jointed thumbs; after puberty, testicles may be enlarged, a condition known as macroorchidism.
Low muscle tone.
Fragile X is the most common single gene cause of autism and the most common inherited cause of intellectual disability.
Changes in the FMR1 gene, officially known as the “fragile X mental retardation 1” gene, cause Fragile X syndrome. Normally, FMR1 instructs for a protein called fragile X mental retardation 1, or FRMP. This protein plays an important role in the communication between the nerve cells, in an area called the synapse. Important for a condition called synaptic plasticity, the protein aids in creating the conditions for memory and learning. The protein acts as a shuttle within cells carrying mRNA from the nucleus to the area where proteins are assembled. Many of the proteins are related to nerve action.
One area of the gene has the trinucleotide sequence CGG on the X chromosome. If the repeats are between 29 and 31, the person will be normal for this gene and not affected by the syndrome. The full mutations may have more than 200 CGG repeats and the person will be affected with FXS. The expanded CGG repeat turns off FMR1, disrupting the creation of the fragile X mental retardation 1 protein. This disruption leads to the signs and symptoms of Fragile X. People with 55 to 200 repeats may have a permutation and be intellectually normal but have mild versions of the physical and behavioral attributes such as prominent ears or hyperactivity. About 20% of women with a permutation stop their menstrual cycles before the age of 40. One other situation may occur with permutation; the person may develop fragile X–associated tremor/ataxia (FXTAS), resulting in a progressive condition movement, tremor, memory loss, and mental and behavioral changes.
FRMX1 is inherited in an X-linked dominant pattern and is located on the long arm (q) of the X chromosome at position 27.3.
Because Fragile X is a genetic condition, there is no cure, although several medications have been proposed. Currently, behavior therapy, special education, and physical therapy may help improve the quality of life for individuals with Fragile X.
See also X Chromosome: A Special Topic
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