Dear Doctor Column, April 12, 2004
Fragile X Syndrome Has Wide Range of Symptoms
Question:
My 3-year-old son has been diagnosed with fragile X syndrome. Doctors in our town didn't know what was wrong with him and it finally took a specialist in another city to correctly diagnose him. At least now we know what's wrong. We would very much appreciate any information you could provide us about fragile x.
Answer:
Fragile X syndrome is a heredity genetic disorder. It is different from Down syndrome, another common genetic cause of mental retardation: Down syndrome is caused by an extra chromosome (chromosomes are the structures in cells that contain the genes), while fragile X syndrome is caused by an abnormality in a single gene.
Although fragile X is the single most common inherited cause of mental impairment (ranging from learning disabilities to mental retardation), up to 90% of children with the disorder are either incorrectly diagnosed or remain undiagnosed. The syndrome affects about 1 in 4000 boys and 1 in 8000 girls and occurs in all racial and ethnic groups, according to the March of Dimes.
While many children with fragile X syndrome do not look different from their peers, some have subtle physical signs. These include a long narrow face, large ears, a high arched palate, flat feet, and overly flexible joints (especially the fingers). Some of these features do not become apparent until after puberty, when boys tend to develop enlarged testicles. Speech and language problems can include involuntary repetition of words or phrases, inability to move mentally from one idea to another, poor language content, and dropping of letters or syllables when speaking.
Although most boys with fragile X syndrome have mental retardation or serious learning disabilities, only about 30% to 50% of affected girls do; girls with fragile x syndrome also have fewer physical signs of the disorder. Emotional and behavioral problems are common in both sexes.
Fragile X syndrome is caused by a mutation on the X chromosome. Women have two X chromosomes; males have one X and one Y chromosome. In 1991, scientists discovered the gene (called FMR1) that causes fragile X syndrome. This gene, located near the end of the X chromosome, contains between 6 to 50 repetitions of 3 bases (called CGG repeats). If the number of repeats increases from 50 to 200, this results in a pre-mutation. An increase of more than 200 is called a full mutation and will result in fragile X syndrome.
The function of the fragile X gene is to produce a protein (called FMRP) that is important in the development and functioning of the brain. No protein is produced in individuals with the full mutation. Those who have the pre-mutation are carriers for this condition and generally do not show symptoms of the disorder.
Fathers who carry the pre-mutation gene, pass it on to all their daughters, but none of their sons. Each child of a woman who carries the gene has a 50% chance of inheriting the gene. Fragile X pre-mutation can be passed silently down through generations in a family before a child is affected by the syndrome.
A new test to diagnose fragile X was developed in 1992 and can detect both carriers and affected individuals. The test is available at most U.S. medical centers.
A health-care provider may recommend a child be tested for fragile X syndrome if he has mental retardation, developmental delay or autism, especially if the child has physical or behavioral characteristics of fragile X syndrome, or if there is a family history of fragile X syndrome or mental retardation of unknown cause. A health-care provider also may recommend testing if a woman who is planning a pregnancy has a family history of fragile X syndrome or mental retardation or if she shows possible symptoms of fragile X syndrome.
There is currently no cure for fragile X syndrome, although appropriate education and medications can help maximize the potential of each child. Treatment of the disorder includes special education, speech, occupational and sensory integration training, and behavior modification programs. Genetic counseling is often beneficial to families.
Significant progress has been made in understanding mechanisms and potential treatments for inherited diseases caused by a single gene, such as fragile X. Current medical research focuses on:
- gene therapy — studying the gene that causes fragile X to determine whether a healthy gene can be inserted into the DNA of affected individuals, thereby replacing the ineffective gene;
- protein replacement therapy — studying the protein product lacking due to the gene mutation in hopes that the protein can be supplemented from an external source; and
- psychopharmacology — treating symptoms of the disorder with medications.
For more information about fragile X syndrome, contact your local March of Dimes chapter or the following organizations: