Autism-World

The purpose of these recommendations is to provide general guidelines to aid clinicians in making referrals for fragile X syndrome testing.

Individuals for Whom Testing Should Be Considered

• Individuals of either sex with mental retardation, developmental delay, or autism, especially if they have (a) any physical or behavioral characteristics of fragile X syndrome, (b) a family history of fragile X syndrome, or (c) male or female relatives with undiagnosed mental retardation.
• Individuals seeking reproductive counselling who have (a) a family history of fragile X syndrome or (b) a family history of undiagnosed mental retardation.
• Fetuses of known carrier mothers.
• Patients who have a cytogenetic fragile X test result that is discordant with their phenotype. These include patients who have a strong clinical indication (including risk of being a carrier) and who have had a negative or ambiguous test result, and patients with an atypical phenotype who have had a positive test result.

Population Screening

Population carrier screening is not recommended at this time except as part of a well-defined clinical research protocol. The DNA test is very accurate, but it is important to ensure that effective means are in place to adequately inform tested populations of the meaning and implications of results. The nature of the FMR1 mutation and its inheritance are complex, and testing necessitates appropriate follow-up counseling.

Approaches to Testing

• DNA analysis is the method of choice if one is testing specifically for fragile X syndrome and associated trinucleotide expansion in the FMR1 gene.
• If the etiology of mental impairment is unknown, DNA analysis for fragile X syndrome should be performed as part of a comprehensive genetic evaluation which includes routine cytogenetic analysis. Cytogenetic studies are critical since constitutional chromosome abnormalities have been identified as frequently or more frequently than fragile X mutations in mentally retarded individuals referred for fragile X testing.
• For individuals who are at risk due to an established family history of fragile X syndrome, DNA testing alone is sufficient. If the diagnosis of the affected relative was based on previous cytogenetic testing for fragile X syndrome, then at least one affected relative should be included in DNA testing.
• Prenatal testing of a fetus is indicated following a positive carrier test in the mother. When the mother is a known carrier, DNA testing can be offered to determine whether the fetus inherited the normal or mutant FMR1 gene. Results from CVS testing must be interpreted with caution because the methylation status of the FMR1 gene is often not yet established in chorionic villi at the time of sampling. CVS, while a standard technique for prenatal diagnosis, may lead to a situation where follow-up amniocentesis is necessary to resolve an ambiguous result.

Technorati : Fragile X Syndrome

This entry was posted on Friday, September 14th, 2007 at 2:44 pm and is filed under Fragile X Syndrome.