Fragile X Carrier Screening
What is Fragile X Syndrome?
Fragile X syndrome is the most common cause of inherited intellectual disability, affecting approximately one in 3,600 males and one in 4,000-6,000 females.1 It can occur in any ethnic group. Intellectual disability may range from learning disabilities to severe mental retardation and autism. Physical characteristics are often more pronounced in adult males and may include macrocephaly, enlarged ears, and a long face with a prominent chin. Approximately 50% of females with a full mutation have borderline or mild intellectual disability.2
Fragile X syndrome is caused (in >99% of cases) by an expansion of an unstable CGG repeat in the FMR1 gene. Most individuals have a CGG repeat size between 5-44 repeats, which is considered normal. Those with fragile X syndrome have a repeat size greater than 200, which is referred to as a full mutation.3
An estimated one in 259 females and one in 755 males in the general population have an FMR1 premutation with 55 to 200 CGG repeats.4 Fragile X premutation carriers do not experience intellectual disability, but they may be affected by other symptoms. Approximately 21% of female premutation carriers experience premature ovarian insufficiency. Approximately 40% of male and 8-17% of female premutation carriers over the age of 50 report experiencing symptoms of Fragile X-associated tremor/ataxia syndrome (FXTAS).5,6 FXTAS is a neurodegenerative disorder characterized by cerebellar ataxia, intention tremor, progressive cognitive decline, and psychiatric disorders.
How is Fragile X Syndrome Inherited?
Fragile X syndrome is inherited in an X-linked manner. Female premutation carriers are at risk to have children with Fragile X syndrome. If a female premutation carrier passes the X chromosome with the premutation to a child, it may remain stable or it may expand, possibly to a full mutation. The risk of expansion depends in part on the number of maternal CGG repeats and the presence of interspersed AGG repeats. The smallest premutation that has been reported to expand to a full mutation in one generation is 56 repeats.7,8
Reporting of Fragile X Testing Results: