Fragile X syndrome – genetic testing for fragile X syndrome (FXS)

Fragile X syndrome – genetic testing for fragile X syndrome (FXS)

Fragile X syndrome is a genetic disorder that is the most common genetic cause of autism and intellectual disability.

The disorder is also known as Martin-Bell syndrome, named after the two researchers (Julia Bell and Purdon Martin) who first detected the link between hereditary and intellectual disabilities, and discovered that the two are connected to a fault in a certain gene. This gene was only identified in 1969, the disorder was named “fragile X syndrome” after the “broken” appearance of the chromosome where this gene is located.


Fragile X syndrome can affect people of all populations and ethnic descents. It occurs in 1 in 8,000 females and 1 in 4,000 males.


What are the symptoms?

The most distinct characteristic of fragile X syndrome is intellectual impairment. Around 80% of people with FXS have an IQ lower than 75.

The first detected symptoms are usually a slight developmental delay in early infancy, and the intellectual disability is only detected at a later stage. Around 70% of people with this disorder have distinct autistic characteristics, the remaining 30% have disabilities on the autistic spectrum. 

The intellectual disability is often more severe in boys than in girls. Girls with FXS have milder intellectual and behavioral disabilities, that may sometimes present as mild learning difficulties.

In addition to the intellectual impairment, fragile X syndrome has distinct physical characteristics. In boys, these include large, elongated, and protruding ears, an elongated face, enlarged head size, and enlarged testicles (up to twice the average size). In girls, characteristics include large protruding ears and sometimes a prominent jaw. Many women with this condition experience premature menopause (before the age of 40).

The disorder affects many other organ systems including the cardiovascular system, the skin, muscles, digestive system, feet and more.

What Genes does fragile X syndrome affect?

Fragile X syndrome is caused by mutations in the gene FMR1 (short for Fragile X mental retardation). This gene is located on the X chromosome. 


Normally, the promoter for this gene contains a triple sequence repeated between 29 – 31 times.

Too many repeats of this sequence can cause fragile X symptoms. The more repeats, the more severe the disorder. More than 200 repeats are enough for a diagnosis of fragile X syndrome.


How is Fragile X syndrome inherited?

The inheritance of Fragile X syndrome is recessive and X-linked. This means that one of the mother’s X chromosomes contains a mutation in one of the alleles, while the father is not a carrier.

In this case there is a 50% chance of passing down the defected allele to the child. If the allele is not inherited, the child will be healthy. However, if the allele is inherited, baby boys will suffer from the disorder and baby girls will either suffer from the disorder of be carriers, and in any case will suffer from less severe symptoms than boys.

The second form of inheritance is passed down from the father or mother when the mutation is has occurred only in the egg or sperm, there are also different combinations of these two inheritance forms. For instance, of the mother is a carrier of the defect gene in one X chromosome but has a second chromosome with a premutation, or cases of a carrier mother whose partner carries the pre-mutational gene.

It is important for women to undergo genetic testing for fragile X syndrome before the pregnancy, to prevent this disorder. If the test was not performed before the pregnancy, the disorder can be detected during the pregnancy through amniocentesis or chorionic villus sampling (CVS).

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