Genetics - Fragile X syndrome

Question 1

Definition

Answer 1

Fragile X syndrome is caused by a mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome. The FMR1 gene codes for the fragile X mental retardation protein, which plays a role in cognitive development in the brain.

Question 2

Inheritance

Answer 2

• X-linked but unclear whether it is dominant or recessive
• Males always affected but females can vary in how much they are affected
• This is because females have a spare normal copy of the FMR1 gene on their other X chromosome. When the mother is phenotypically normal, the affected child may have inherited the X chromosome from their mother, or it may result from a de novo (random) mutation.

Question 3

Signs

Answer 3

Fragile X syndrome usually presents with a delay in speech and language development. Other features are:
- Intellectual disability
- Long, narrow face
- Large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- ADHD
- Autism
- Seizures

Question 4

Treatment

Answer 4

No cure
Management is supportive and involves treating the symptoms. This involves MDT to support the learning disability, manage autism and ADHD and treat seizures if they occur. Life expectancy is similar to the general population depending on associated disabilities and complications.