Genetics
Fragile X syndrome is the most common inherited form of mental retardation. It is an X-linked dominant condition that is associated with an expansion of a trinucleotide repeat sequence (CGG)n located on chromosome Xq27.3. This expansion results in a failure to express the FMR1 gene product, which is required for normal neural development. In individuals with Fragile X syndrome, the FMR1 allele contains over 200 copies of the (CGG) trinucleotide repeat sequence. Risk for Fragile X syndrome is determined by the length of the repetitive (CGG) sequence;
- Normal (<40 CGG repeats)
- Intermediate or Gray Zone (41 – 60 CGG repeats)
- Premutation (61-200 CGG repeats)
- Full Mutation (more than 200 CGG repeats)
Incidence
- Affects approximately 1 in 3,600 males and approximately 1 in 4,000-6,000 females
- It is estimated that 1 in 250 females and 1 in 800 males are premutation carriers
- Fragile X syndrome is an X-linked dominant condition
- Women with ovarian failure or an elevated follicle-stimulating hormone level before 40 years of age without a known cause should be screened to determine whether they have the fragile X premutation
Major Phenotypic features
- Childhood onset
- Mental deficiency
- Dysmorphic facies
- Male maro-orchidism
- Affected females present with variable phenotypic features due to random X inactivation
Facial Features
- Elongated face
- Large or protruding ears
- Prominent jaw and forehead
Clinical Management
Currently, medical treatment for Fragile X syndrome is not available. Patients may benefit from behavioral therapy, special education, medication, and treatment of physical abnormalities.