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Sunday, 24 March 2013

Fragile X Syndrome


Fragile X syndrome is an inherited condition that can cause learning disabilities in sufferers. The condition is cause by a mutation to the FMR1 gene on the X chromosome. Because of this it is more prevalent in males (who only inherit one X chromosome, from their mother, so if it is faulty, will have the condition) however, it can also be inherited by females. Fragile X is also the largest genetic cause of autism accounting for 5% of cases. Around 1 in 4000 males and less than 1 in 6000 females are estimated to suffer from fragile X.


The mutation of the FMR1 gene is due to the number of repeats of the gene, which has the sequence CGG (the triplet: cytosine, guanine, guanine nitogenous bases that codes for the amino acid arginine in the proteins created by translation of the sequence). People with less than 45 repeats do not suffer from fragile X. Those with between 55 and 200 repeats are said to have a permutation, as their gene is unstable, and could cause the syndrome in their descendants, these people can also suffer from fragile X associated disorders. In female carriers, during the division to form egg cells, extra repeats of CGG can be added, and a child that develops from that egg is likely to be a sufferer. Around 1 in 250 women may be carriers and around 1 in 800 men. In people with over 200 copies of the CGG sequence, the gene is methylated, this means that a methyl group (1 carbon and 3 hydrogen atoms) is added to either C or A nucleotides, this process ‘silences’ the gene so that it is no longer expressed.

The FMR1 gene codes for a protein known as FMRP (fragile X mental retardation protein). This protein is involved in the formation of dendritic spines. Dendritic spines are developed by neurons (nerve cells) and are used to help transmit electrical signals and to increase the number of connections between neurons. Without this protein, people can have severe intellectual impairment, including a decline in memory with age, and children often learn 55% slower than their unaffected peers; however, some people with fragile X have a normal IQ.

Fragile X sufferers often have a characteristic phenotype, including large protruding ears, a long face, hyperextensible fingers and thumbs, flat feet, low muscle tone (hypertonia), macroorchidism (large testes in post-pubescent men) and a single palm crease. Fragile X also has an effect on vision and common problem include strabismus (lazy eye) or refractive errors. Sufferers are also at risk of suffering from seizures, but these can be treated with medication.


Fragile X syndrome can also affect emotions and behaviour in addition to IQ, sufferers can also have social anxieties such as poor eye contact and difficulties forming per relationships. Up to 75% of male sufferers where categorised as having excessive shyness, and many suffered from panic attacks. This is thought to be due to challenges that sufferers have with recognising faces of people they have met and also due to hypersensitivity to noise (so a dislike of crowds). Obsessive or anxiety based behaviours are also common such as hand flapping or biting(self-injury), perseveration (repeating an action even when a stimulus has been removed), self-talk and aggression. Most males and around 30% of females with the full mutation for fragile X have ADHD so display symptoms such as hyperactivity and inattentiveness.

Associated disorders of fragile X syndrome include autism, FXTAS and FXPOI. FXTAS is fragile X associated tremor/ataxia syndrome, which is an adult onset disorder which can lead to dementia, mood instability, cognitive decline and memory loss, tremors, ataxia (loss of balance) and symptoms of Parkinson’s disease such as shuffling movement. FXPOI is fragile X associated primary ovarian insufficiency, and includes symptoms similar to menopause such as hot flushes, unusual menstruation, FXPOI can lead to decreased fertility or infertility, and occurs in around 20% of women with fragile X or carriers of fragile X.
We can screen for fragile X in pregnancy by testing the amniotic fluid or CVS (chorionic villus sampling), however this cannot accurately determine whether a child will develop any of the associated disorders.

There is no cure for fragile X at the moment, however, with educational and emotional support, many affected people are able to cope with related disorders, and some medications or therapies can help alleviate certain symptoms. Other options could include gene therapy to demethylate genes using drugs or blocking receptors for mGluR5 a protein which, when FMRP is missing, causes over-activity of the brain, and by inhibition can reduce seizures and learning delays.


Base pairs, are found as part of the nucleotides in DNA, A-adenine which pairs with T-thymine and C-cytosine with G-guanine.
Nucleotides, the molecules which make up DNA and are made from a phosphate group, 5-carbon sugar and an organic base (see base pairs)
Phenotype, is the observable, physical and behavioural characteristics of an organism.


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