Fragile X Syndrome:

Fragile X syndrome (Fragile X) is the most common cause of inherited mental retardation (MR). As an X-linked dominant disorder with reduced penetrance, it is caused by an expansion of a CGG repeat in the first exon of the FMR-1 gene. Normal individuals have 5 to 46 repeats, unaffected carriers have premutations of 47 to 200 repeats and affected individuals have full mutations of over 200 repeats.  There is a gray-zone of indeterminate risk from 36 to 46 repeats.  Premutation carriers have a risk of having offspring with full mutations that is dependent on the number of repeats. Males with full mutations have developmental and speech delays, dysmorphic faces, large or prominent ears, macroorchidism and moderate to severe mental retardation. About 50% of females with full mutations have learning disabilities or mild to moderate mental retardation.

REASONS FOR REFERRAL:

• Individuals with unexplained developmental delay or mental retardation. Both standard chromosome analysis and DNA testing for Fragile X are recommended. This approach allows the diagnosis of chromosome abnormalities which occur in these individuals with MR as frequently as Fragile X syndrome.

• Carrier determination.

• Prenatal diagnosis.

TESTING METHODOLOGY:

• Southern blot analysis of the CGG region of the FMR-1 gene to identify the expanded alleles and methylation status. PCR assay to determine specific repeat number of repeats in premutation carriers.

SPECIMEN REQUIREMENTS:

• Blood EDTA (purple top) tubes:  

            Newborn: minimum 1-2 mL          

            Child/Adult: prefer 2 tubes of 3-5 mL

• Prenatal testing: Please contact the laboratory for instructions.

TURNAROUND TIME: 3 weeks

CPT CODES: