Fragile X syndrome is the most common known inherited cause of intellectual disability and autism. Features of fragile X syndrome vary widely but can include mild to severe cognitive delays, seizures, behavioral differences such as perseverative speech and hand flapping, and characteristic facial features such as large ears and a long face. About 1 in 4,000 males and 1 in 5,000 to 8,000 females has fragile X syndrome. The molecular basis for fragile X syndrome is an increased number of trinucleotide CGG repeats in the 5′ promoter region of the FMR1 gene. FMR1 alleles can be further categorized based on the number of CGG repeats, and premutation alleles may expand from parent to child to a full mutation that can cause features of fragile X syndrome. In addition, people with premutations may develop fragile X-associated Tremor/Ataxia Syndrome (FXTAS) and women may develop fragile X-associated Primary Ovarian Insufficiency (FXPOI).
Table 1: Categories of triplet repeat mutations in the FMR1 gene.
|REPEAT NUMBER||ALLELE CATEGORY||CLINICAL FEATURES||LIKELIHOOD TO EXPAND|
|45-54||Intermediate||None||Small likelihood to expand by usually a small number of repeats|
|55-200||Premutation||FXTAS symptoms over age 50 (46% of males and 17% of females); FXPOI (15-20% of females)||Unstable; likelihood varies based on total repeat number and AGG interruptions; may expand to full mutation|
|>200||Full mutation||Fragile X syndrome||Unstable|
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