FRAGILE X SYNDROME

Fragile X is a genetic syndrome that is the most widespread single-gene cause of autism and inherited intellectual delay. The syndrome results in a spectrum of disabilities ranging from mild to severe. The genetic anomaly associated with this disease is the result of a mutation in the FMR1 gene located on the X chromosome. Because the mutation is dynamic, it can change in severity from generation to generation, from person to person, and even within a given person.

The characteristic features of Fragile X in boys includes prominent ears, a long face, delayed speech, large testes, hyperactivity, behavior issues, gross motor delays, and autistic-like behaviors.

Only about half of all females who carry the genetic mutation have symptoms. Intellectual and speech delays have been observed in females with Fragile X. About 20% of women who are carriers for a Fragile X premuation are affected by Fragile X-related primary ovarian insufficiency (FXPOI), which is defined as menopause before the age of 40. The number of CGG repeats affects the penetrance and age of onset. Premature menopause is more common in premutation carriers than in women with the full mutation. Females with a full mutation have a greater risk of passing the mutation to their offspring.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by problems with movement and thinking ability. FXTAS is a late-onset disorder, usually occurring after age 50, and its signs and symptoms worsen with age. This condition affects males more frequently and severely than females. Affected individuals have areas of damage in the cerebellum, the part of the brain that controls movement. This damage leads to movement problems and other impairments associated with FXTAS. Symptoms include tremors, ataxia, parkinsonism, reduced sensation, numbness or tingling and weakness of muscles, and short term memory loss.

Fragile X is confirmed when the number of CGG repeats in the FMR1 gene are found to be higher than normal. Premutation or carriers possess a range of 55-200 CGG repeats. Patients with a full mutation are found to have 200 or more CGG repeats. See link to table. This assay uses PCR and capillary electrophoresis for fragment analysis across the CGG region to determine allele size. If this assay yields a normal result (5-44 repeats) no further testing will be required. In both male and female patients where the initial test does not yield a normal allele pattern, Southern Blot analysis will be performed to identify large expansions of the CGG repeat region.

CPT Code: 81243 and 81244

Specimen Requirements: 2-5 mL Blood- EDTA tube (Lavender Top)

Turn-around-time: 28 days

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