X-Linked Mental Retardation Health Article

Diagnosis

The diagnosis of XLMR should be considered in all children with autistic behaviors, mental retardation, developmental delay, or unexplained speech delay; 80–90% of patients with fragile X syndrome are not yet correctly diagnosed. Because the symptoms of fragile X can be quite subtle, especially in young children, and because it is so frequent in the general population, many medical specialists recommend testing for fragile X syndrome. This is, however, not a routine screening test for all children. Testing for FMR1 mutation is possible in people of any age and even before birth.

A variety of diagnostic tests based on DNA, chromosomal, or protein analysis is available. Chromosomal tests look for the fragile, or broken, portion of the X chromosome under a microscope, but are generally not very sensitive. Protein tests measure the amount of FMR protein produced by the cells and can determine the severity of the disorder. A DNA-based test to diagnose fragile X was developed in 1992 and is based on detecting an increased number of repeating units. This test is quite accurate, and it can detect both carriers and fully affected individuals. Samples from blood, hair root, or a scraping from inside the cheek can be used to carry out the test. In a pregnant woman, amniotic fluid or cells from the placenta, called chorionic villus, are used to detect the mutation. Similarly, genetic testing can be done in specialized laboratories for the other common gene mutations associated with XLMR, such as Rett's syndrome.

Treatment

Currently, there is no cure for any of the conditions associated with XLMR. Best results are obtained when medications are combined with educational, social, and occupational therapy. Early intervention when the child's brain is still developing is advocated in order to maximize its long-term potential. A team comprising of a neurologist, genetic specialist, psychologist, behavioral specialist, physical, occupational, and speech therapists should work with the family and caregivers to ensure that the child receives appropriate therapy based on individual needs. This team can also assess the patient's level of independence and ensure appropriate transition from adolescent to young adult.

The U.S. Food and Drug Administration Agency (FDA) has not approved any specific medication for treatment of fragile X or its symptoms. But several medications have been tried on an empiric basis to ameliorate specific symptoms and problems associated with this disorder. Seizures and mood instability can be treated with drugs used primarily in epilepsy, such as carbamazepine, valproate, gabapentin, and topiramate.

The Individuals with Disabilities Act of 1997 ensures free education for children with mental retardation and special cognitive needs until high school or until they reach 21 years. This law also ensures that children are taught in a non-restrictive environment tailored to their special needs. Speech therapists can help in language acquisition and devise innovative ways for nonverbal communication. Occupational therapists can assist the child with adaptive equipment to help overcome physical disabilities. Physical therapists help in designing programs and activities to promote posture, gait, and balance. Behavioral therapists can work with the family and the child in identifying strategies and coping skills to deal with social situations and avoiding aggression.

The Fragile X Research Foundation (FRAXA) funds several endeavors to help find a cure for this disease. Ongoing research is focused on repairing the defective gene, replacing the defective gene, supplying the deficient protein, or substituting the deficient protein with another protein.

Prognosis

Children with fragile X syndrome have a fairly normal life expectancy. With early diagnosis and treatment, they can grow into independent individuals. Similarly, children with Rett's syndrome usually survive to adulthood and middle age.

BOOKS

Fenichel, Gerald M. Clinical Pediatric Neurology, 4th edition. Philadelphia: W.B. Saunders Company, 2001.

PERIODICALS

Check, Erika. "The X Factor." Nature 434 (March 2005): 266–267.

Ropers, Hilger H., and Ben C. J. Hamel. "X-linked Mental Retardation." Nature 6 (Jan. 2005): 46–57.

Wiesner, Georgia L., Suzanne B. Cassidy, Sarah J. Grimes, Anne L. Matthews, and Louise S. Acheson. "Clinical Consult: Developmental Delay/Fragile X Syndrome." Primary Care: Clinics in Office Practice 31 (2004): 621–625.

ORGANIZATIONS

International Rett Syndrome Association. 9121 Piscataway Road, Clinton, MD 20735. (800) 818 RETT. (April 24, 2005.) <http://www.rettsyndrome.org>.

National Fragile X Foundation. P.O. Box 190488, San Francisco, CA 94119. (800) 688 8765. (April 24, 2005.) <http://www.nfxf.org>.

National Institute of Child Health and Human Development. P.O. Box 3006, Rockville, MD 20847. (800) 370 2943. (April 24, 2005.) <http://www.nichd.nih.gov>.

OTHER

Fragile X Research Foundation (FRAXA). 45 Pleasant Street, Newburyport, MA 01950. (978) 462 1866. (April 24, 2005.) <http://www.fraxa.org/>.

National Institute of Child Health and Human Development (NICHD). "Families and Fragile X Syndrome." NICHD Publication No. 03-3402. 2004.

Chitra Venkatasubramanian, MBBS, MD