What is fragile X syndrome?

Fragile X syndrome is the most frequently occurring cause of learning disability. It affects twice as many boys as girls, and the symptoms in boys are usually more severe. It can cause developmental delays in children with other symptoms sometimes similar to autism, and difficulties with language, learning and social interaction as well as emotional and behavioural problems. There are often some physical characteristics associated with the condition but these are difficult to detect in a baby or young child and as a result, diagnosis is often delayed until problems become apparent.

In this IVI blog article, we explain what causes fragile X syndrome, how it is diagnosed and treated and what help is available. We also explain how genetic testing has advanced in recent years to the extent that, under the right circumstances, this and other monogenic disorders can be detected before pregnancy.

What causes fragile X syndrome?

Fragile X syndrome is a monogenic disorder, that is, one which results from a single faulty gene. Its location is on the X chromosome, of which girls have two and boys have one, with one Y chromosome. The precise gene which causes the condition is the FMR1 gene; it makes the FMR protein which is essential for normal brain development. In cases of fragile X, production of this protein is impaired or completely absent. This explains why symptoms are commonly more severe in boys, since their only X chromosome carries the faulty gene, whereas in girls, there is likely to be one X chromosome which is healthy.

It is also possible for an individual to inherit the gene but not have any symptoms. These carriers can pass the gene on to their children. A woman has a 50% chance of passing on the gene to any of her children, whereas a man can only pass it on to his daughters.

How is fragile X syndrome diagnosed?

In 1991, the discovery of the gene which causes the syndrome led to the development of DNA testing which is used to identify both carriers and affected individuals. Although there are frequently, though not always, physical characteristics such as a long, narrow face and prominent ears and jaws, these are not easily detectable at an early age. The average age at which diagnosis takes place for boys is 36 months, and for girls around 42 months.

The diagnostic test is a DNA blood test called the FMR1 DNA test. In the UK, this test is carried out at genetic centres which are available to patients referred by a hospital specialist via their GP. The blood sample will probably be taken in a hospital and passed on to the genetic testing centre. The UK’s Fragile X Society offers advice on getting a diagnosis and a complete list of all the UK genetic centres. The NHS has also published advice about genetic testing.

How is the condition treated and what help is available?

Unfortunately, fragile X syndrome cannot be cured. However, various treatments and therapies can help a child to manage social and behavioural issues. These could include:

• Special education to help with learning;
• Language and speech therapy;
• Help with managing daily tasks through occupational therapy;
• Medication that can help prevent seizures and improve symptoms such as hyperactivity and attention deficit.

A good deal of online information and advice, including a helpline service, support workers and online publications are available in the UK through the Fragile X Society.

Can fragile X syndrome be prevented?

We have seen how the syndrome can be detected once it exists through diagnostic genetic testing, and it can also be detected during pregnancy. But could it be prevented in the first place? Happily, the answer is yes and this is where assisted reproduction techniques come into their own. Once you have established that you or your partner have a chance of passing on chromosomal alterations or monogenic diseases such as fragile X syndrome to your offspring, you can prevent this from happening by means of Preimplantation Genetic Testing for monogenic diseases (PGT-M).

What is PGT-M and how does it work?

In a nutshell, this is a test to identify genetic and chromosomal alterations in embryos to ensure that only those which are genetically normal and free of hereditary diseases are implanted into the womb. It can only be carried out in conjunction with in vitro fertilisation (IVF) and sperm microinjection (ICSI). These are the stages of the process:

• Genetic testing is carried out on the carrier parents so that as much information as possible about the heritable condition is obtained.
• Embryos are obtained using the well-established IVF process. This is essential in order for the embryos to be studied for diagnosis, even though the prospective parents may not have any fertility problems which would normally prompt the intervention of IVF.
• When the embryo has reached blastocyst stage, an embryo biopsy is performed where a small sample of cells is extracted from the trophoblast (the future placenta) without damaging its future development. The embryos are then frozen until the analysis has been completed.
• After the genetic study has been carried out, the embryos that are genetically normal but also healthy (free of disease), can be inserted into the maternal uterus.

Fragile X syndrome (amongst other autosomal recessive diseases), autosomal dominant diseases and genetic diseases linked to the X chromosome, can be identified with PGT-M. In IVI, we have a dedicated PGT laboratory in which each case is individually studied. We have accumulated such a wealth of experience in this field that we have become a benchmark in Spain for the quality of our processes, to the extent that other health centres request our services for carrying out these tests.

Technical expertise aside, the human aspect of the success of this technique is its most important success story. People who long to become parents, but have reason to fear passing on a genetic condition, no longer need to deny fulfilling that dream and can look forward with confidence to a future as parents.