Fragile X syndrome
- Definition: an X-linked dominant disease caused by a CGG trinucleotide repeat expansion in the FMR1 gene (fragile X mental retardation 1 gene) during oogenesis. This leads to its hypermethylation, which silences the gene and renders it unable to express its physiological gene product.
- Epidemiology
- Second most common genetic cause of intellectual disability (after trisomy 21)
- Most common inherited cause of intellectual disability, as trisomy 21 mostly occurs sporadically
- Clinical features: The clinical presentation varies depending on the number of trinucleotide repeats.
- 50–200 repeats (premutation): ataxia, primary ovarian insufficiency, tremor
- 200 repeats (full mutation):
- Intellectual disability of varying severity
- Delayed language development
- Behavioral features: autistic behavior, hyperactivity, anxiety
- Characteristic facial anomalies
- Long and narrow face
- Prominent forehead and jaw
- Large everted ears
- Hypermobile joints
- In men: postpubertal macroorchidism (enlarged testes; rarely occurs prior to puberty)
- Mitral valve prolapse: can lead to mitral regurgitation
- Above-average head circumference
Mnemonic
Fragile X: “X-tra large” ears, testes, and face in these patients.