Definition of Fragile X Syndrome
Fragile X syndrome (FXS), also known as the Martin-Bell syndrome, is a genetic condition that causes intellectual disability with lifelong difficulties. FXS is named Fragile X syndrome because, when looked at through a microscope, part of the X chromosome looks “broken” or “fragile”. This syndrome is genetic, meaning that it is passed down from parents to children. Although Fragile X syndrome can affect both genders, it has been noted to affect males more frequently and with higher severity than in females. The main reason why it’s less prevalent or less severe in females is that some females may not exhibit some features of the Fragile X syndrome e.g., they may not show behavioural, physical or cognitive features of FXS. Also since the gene mutation is X-linked, males are more severely affected than females (CDC, 2001; National Fragile X Foundation; Raspa et al., 2017; & Ray et al., 2017).
Causes of Fragile X Syndrome
Fragile X syndrome is caused by a change to or mutation of a gene on the X-chromosome called the FMR1 gene. This gene produces a protein needed for normal development which helps the brain to function normally. If this gene is changed or altered in any way, it cannot produce its normal protein, which can then lead to Fragile X syndrome. In some rare instances, there is the possibility of those affected may either have the FMRI gene partially or completely missing either having a partially or completely missing.
Fragile X syndrome is inherited in a way that is known as 'X-linked', as the changed gene is on the X chromosome. This means that men with Fragile X syndrome are often more severely affected than women. This is because men only have one X chromosome, whereas women have two X chromosomes, only one of which is changed.
Types of Fragile X Syndrome
There are three main types of Fragile X syndrome disorders caused by changes to the FMRI gene (CDC, 2001; National Fragile X Foundation; Raspa et al., 2017; & Ray et al., 2017). These changes are what scientists usually refer to as mutations.
- Fragile X syndrome – this is caused by a full mutation of the FMR1 gene which typically makes a protein the called Fragile X mental retardation protein (FMRP) which is needed for normal brain development. This means that people who are affected are not making the FMRP because the FMRI gene has been turned off, resulting in a full mutation of the gene.
- Fragile X-associated primary ovarian insufficiency (FXPOI) – this is the condition where ovarian function is not normal. Those who exhibit this type are due to premutation or excess number of mutations in the FMRI gene. This means those affected by this condition may not have fully functioning ovaries which may lead to early menopause or infertility.
Fragile X-associated tremor/ataxia syndrome (FXTAS) – this is a neurodegenerative disorder with adult-onset or also referred to as a nervous system disorder that may sometimes lead to tremors and challenges with walking, balance (also called ataxia), memory and mood disorders among older adults.
Symptoms of Fragile X Syndrome
Symptoms of the Fragile X syndrome vary from challenges in physical, behavioural, emotional and developmental aspects of those affected. Behavioural characteristics evident in males may also be evident in females, however, in most instances affected females may exhibit milder intellectual disability, behavioural and physical features of the syndrome.
Behavioural symptoms:
Intellectual disabilities and challenges:
- Delayed development, including challenges with speech, language, and communication.
- Intellectual disability and learning challenges.
Distinctive physical features:
- Some affected males may exhibit signs such as having a protruding forehead, a long narrow face, and/or large testicles (also referred to as “macroorchidism”) in post-pubertal males
- Unusually large ears
- Unusually soft skin
Connective tissue complications:
- Feet that are, or seem, flat without the middle arch
- High arched palate
- Joints that are hyper-flexible
- Fingers that are double-jointed
(CDC, 2001; National Fragile X Foundation; Raspa et al., 2017; & Ray et al., 2017)
References
Centers for Disease Control and Prevention (2021, June 1). Data and Statistics on Fragile X Syndrome. CDC.
National Fragile X Foundation (n.d.). Fragile X 101. National Fragile X Foundation.
Raspa, M., Wheeler, A. C., & Riley, C. (2017). Public Health Literature Review of Fragile X Syndrome. Pediatrics, 139(3), S153-S171.
Ray, P., Singh, A., Dash, J. K., Sahoo, P. K., & Dash, J. K. (2017). Fragile X Syndrome: A Rare Case Report with Unusual Oral Features. Contemporary Clinical Dentistry, 8(4), 650-652.
