Fragile X syndrome
Fragile X syndrome is a genetic condition causing developmental delays, learning disabilities, and cognitive impairment, with males typically more severely affected than females.
Overview
Fragile X syndrome is a genetic condition that causes a range of developmental problems. Affected individuals usually have delayed development of speech and language by age 2. Most males with the syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled.
Symptoms
Common behavioral and cognitive symptoms include:
- Anxiety and hyperactive behavior (fidgeting or impulsive actions)
- Attention deficit disorder (ADD)
- Features of autism spectrum disorder
- Seizures (occurring in about 15 percent of males and 5 percent of females)
Characteristic physical features, which become more apparent with age, include large ears, a prominent jaw and forehead, unusually flexible fingers, and in males, enlarged testicles (macroorchidism) after puberty.
Causes & Risk Factors
Mutations in the FMR1 gene cause fragile X syndrome. This gene produces a protein called FMRP, which regulates other proteins and is critical for the development of synapses (connections between nerve cells).
Nearly all cases are caused by an expansion of the CGG triplet repeat within the FMR1 gene:
- Normal: 5 to 40 repeats.
- Fragile X syndrome: More than 200 repeats, which silences the gene and prevents the production of FMRP.
Individuals with 55 to 200 repeats have an FMR1 gene premutation. While often intellectually normal, they may experience mild physical features, emotional problems, or an increased risk for fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS).
Inheritance
Fragile X syndrome is inherited in an X-linked dominant pattern. In females, a mutation in one of the two copies of the gene is sufficient to cause the disorder. In males, a mutation in their single X chromosome causes the disorder. Women with the premutation have an increased risk of having a child with the syndrome, as the repeat number can expand in cells that develop into eggs.