Fragile X syndrome is the world’s leading cause of inherited intellectual disability. It is also the leading identifiable cause of autism. About 6% of autistic people turn out to have fragile X and 50% of pre-school fragile children meet the diagnostic criteria for autism. Fragile X is a genetic disorder that affects about one in 3600 males and one in 5000 females. Around one in 151 women and one in 468 men are carriers. Female carriers have a 50% chance of passing the syndrome on to their children. Male carriers never pass the syndrome onto their sons, but will pass the premutation on to all their daughters. For New Zealand’s population of just over 4.5 million people that means there are up to 12,000 people affected by fragile X. Fragile X is characterized by a wide range of cognitive, behavioral and physical features.
The main cognitive features are:
- Subtle learning difficulties to severe mental impairment
- Delayed milestones (walking, talking, toileting)
- Delayed and repetitive speech
- Attention deficit and hyperactivity
- Difficulties with mathematics
- Strong visual memory
The main behavioral features are:
- Hand biting and hand flapping
- Autistic behaviors
- Difficulty adjusting to change
- Poor eye contact
- Sensory sensitivities (aversion to touch and noise)
- Obsessive-compulsive disorder
- Socially engaging and friendly
- Occasionally aggressive
The main physical features are:
- Long face and large or prominent ears, especially in older males
- Loose connective tissue resulting in low muscle tone, double-jointed fingers, flat feet and heart murmurs
- Frequent ear infections
- Enlarged testicles (macroorchidism) in post-pubertal males
- Epilepsy (affecting 25% of people with fragile X)
- Premature menopause in some female carriers
- A Parkinson’s-like tremor or ataxia syndrome known as FXTAS in some older adult carrier males
Note that not all people with fragile X will display all these symptoms.
Some features, like facial characteristics, tend to develop with age. Most features are more typical of males than females. Females are usually less affected than males, but some features, like difficulties with mathematics, anxiety and obsessive-compulsive disorders appear to be more common in females. For a long time fragile X carriers were thought to be largely free of symptoms of the syndrome. While for many carriers this is the case, increasing evidence shows that some carriers suffer mild symptoms of the disorders, especially problems with anxiety, depression and social cognition. Around 20–25% of adult female premutation carriers experience fragile X-associated primary ovarian insufficiency (FXPOI). This is caused by changes in the FMR1 gene and is a condition in which the ovaries are not functioning at full capacity in a premutation carrier. Recent research has identified a progressive neurological condition that affects male carriers over the age of 50. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is characterised by tremors, balance problems and dementia that worsens with age.
All children exhibiting some of the features listed above, and especially developmental delay or autistic behaviors, should be tested for fragile X.