Fragile X syndrome and learning disability: guide for GP trainees

FXS is the most common inherited cause of learning difficulties.
It is also a single-gene (monogenic) cause of autism spectrum disorder (ASD).
How common?
- Affects about 1 in every 4,000 boys and 1 in every 6,000 girls in the UK.
- Around 125 babies are born with FXS in the UK each year.
- What Does "X-linked" Mean?
  - FXS is inherited in an X-linked pattern:
    - Males (XY) have only one X chromosome → if it's affected, symptoms are usually more severe.
    - Females (XX) have two X chromosomes → the unaffected X can partially "balance out" the other
What causes it?
- A change (repeat expansion) in a gene called FMR1 on the X chromosome.
- This change causes the gene to stop working properly.

Category	CGG Repeats	What It Means
Normal	<45	No risk; gene works normally
Intermediate	45–54	“Grey zone”; usually no symptoms or expansion
Premutation	55–200	Carrier status; gene still works, but can expand in next generation
Full Mutation	>200	Fragile X Syndrome; gene is silenced → ↓ FMRP → symptoms develop

What does this mean for the brain?
- The gene normally makes a protein called FMRP, which is important for brain development.
- Without enough FMRP, children may...

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