- 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
- Intellectual Disability: The most common inherited cause of intellectual disability. It affects males more severely than females.
- Neuropsychiatric:
- Autism spectrum disorder features are very common.
- Anxiety, hyperactivity (ADHD-like symptoms), and impulsive behaviors are characteristic.
- Physical Examination (Classic Buzzwords):
- Long, narrow face with a prominent forehead and jaw.
- Large, everted ears.
- Macroorchidism (enlarged testes), most apparent after puberty.
- Connective Tissue Findings:
- Joint hypermobility.
- Mitral valve prolapse.
- Flat feet (pes planus).
Mnemonic
Fragile X: “X-tra large” ears, testes, and face in these patients.
