Factsheet
Condition:
Fragile X syndrome
Inheritance:
X-linked
Genetic Etiology:
Expansion of a CGG triplet repeat in the promoter region of the FMR1 gene on the X chromosome. Repeat number ranges from 6-40 in the general population. Affected individuals have more than 200 repeats, accompanied by methylation of the promoter which leads to silencing of the gene. Individuals with 40-200 repeats do not display fragile X syndrome, but are at risk of further expansion during germ cell development, and are designated as having "premutations".
Frequency:
Approximately 1/5,000 males
Clinical features:
Fragile X syndrome most often affects males, though some females may manifest signs due to nonrandom X chromosome inactivation. The phenotype includes developmental delay, behavioral problems, long, narrow facies, large head circumference, and macro-orchidism. Premutation females do not have these symptoms, but may experience premature ovarian failure. Some permutation males develop a syndrome of ataxia, tremor, and dementia in late adulthood.
Management:
Supportive care.
Genetic counseling:
Expansion to full mutation only occurs in the female germline; the likelihood is related to the size of the permutation allele. Premutation males will transmit the permutation allele to all of their daughters and none of their sons.