Fragile X syndrome is characterised by moderate intellectual disability in affected males and mild intellectual disability in affected females. Distinctive physical features are sometimes present in affected males, including a large head, long face, prominent forehead and chin, protruding ears, loose joints, and large testes, but these features develop over time and may not be obvious until puberty. Motor and language delays are usually present but also become more apparent over time. Behavioural abnormalities, including autistic behaviours, are common.

Fragile X syndrome has been found in all major ethnic groups and races and is caused by an abnormality (mutation) in the FMR1 gene. FMR1 is a gene located on the X chromosome that produces a protein called FMRP needed for proper cell function. The syndrome became known as the fragile X syndrome because some individuals with the disorder were found to have a segment of their X chromosome that appeared to be broken or fragile (although not completely disconnected). Later, it was learned that the FMR1 gene is located precisely where the X chromosome appears to be “fragile” in affected individuals.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes.

X-linked disorders such as fragile X syndrome are caused by an abnormal gene located on the X chromosome. Females with the abnormal gene may be affected by this disorder. Males are usually more severely affected than females).

It is the absence or severe reduction of the protein made by the FMR1 gene, FMRP, that causes fragile X syndrome. Mutation of the FMR1 gene causes the loss or reduction of FMRP. Nearly all affected individuals have an instability within the gene, leading to an increased number of copies of a portion of the gene called the CGG repeat region (also sometimes called the “trinucleotide” or “triplet” repeat region). When more than 200 repeats are present, abnormal chemical changes occur in FMR1 called methylation. The expansion of the CGG repeat region to greater than 200 repeats, accompanied by methylation of the gene, called a “full mutation,” causes the loss of FMRP, leading to the fragile X syndrome. Fragile X syndrome occurs more often in males and results in a more severe disorder in males.

Mutations in FMR1 are unusual when compared to mutations found in other genes. Some individuals carry between 55 – 200 CGG repeats called a “premutation,” usually without having symptoms associated with fragile X syndrome. These individuals are at risk for having children or grandchildren with fragile X syndrome, however, and are also at risk for two adult onset disorders, fragile X tremor-ataxia syndrome (FXTAS) and primary ovarian insufficiency (POI). These conditions have been termed FMR1-related disorders.

We are here for you.

Dr Chayim Schell-Apacik is a specialist in clinical genetics with over three decades of experience in supporting patients. We offer individualised evaluations, genetic consultation, and testing, with the goal of providing you with genetic information that presents choices and minimises uncertainty, empowering you to make decisions that are most beneficial for you. Please contact us, to find out more.

What is genetic testing?

Genetic testing – sometimes called genomic testing, finds changes in the genetic material that can cause health problems. It is mainly used to diagnose rare and inherited health conditions and some cancers.
You may be offered a genetic test because your doctor thinks

• you or your child might have a health condition caused by a change in the genetic material involving one or more genes or certain chromosomes.
• someone in your family has a health condition that is caused by changes in the genetic material involving one or more genes, or certain chromosomes.
• some of your close relatives have had a particular type of cancer that could be inherited.

At Schell Genetics, we are here to assist you in this process. Please don’t hesitate to contact us.

Learn more about other RARE DISEASES or GENETIC DISORDERS