Che cos'è la sindrome dell'X fragile?

Fragile X Syndrome (FXS) is a genetic condition caused by an alteration on the X chromosome which results in a range of physical, intellectual, emotional, and behavioural symptoms. This alteration causes the FMR1 gene to stop working properly, meaning the protein made from the gene cannot be produced. If you suspect FXS, please see a health professional for genetic testing and diagnosis.

The Fragile X gene and protein are called Fragile X Messenger Ribonucleoprotein 1, which is abbreviated to FMR1. Everyone has the FMR1 gene, but for people with FXS this has an alteration which stops the FMR1 protein (FMRP) from being produced. More about this can be found in the section ‘Genetica dell'X fragile’, which also includes information on the genetic basis for the FMR1 premutation.

Fragile X Syndrome is a rare condition occurring in around 1 in 4000 males and 1 in 6000 females. Both sexes can have FXS, but as females have another X chromosome which can compensate for the altered fragile X chromosome, the condition may look different in men and women. FXS has a wide range of symptoms; no two people with FXS will be the same, and not every individual will have all of the symptoms. As well as having a range of symptoms, people with FXS have lots of strengths including being very friendly, honest, empathetic, and sensitive. Some symptoms will benefit from intervention and therapies, but not every symptom will require professional help. The strengths and positive traits are sometimes overlooked by professionals, so it is important to recognise these too.

Fragile X Syndrome Spectrum

FMR1 is a gene which everyone has, but for people with Fragile X Syndrome (FXS) an alteration stops the creation of the FMR1 protein (FMRP). This protein is used in the development of synapses (the connections between nerve cells). Because proteins have a broad role in the body it means that FXS is a complex condition and a spectrum whereby every person with the condition will have different strengths and difficulties. All of the information below may apply to both genders, but we have additional information on the variable presentation in girls.

Many of those with FXS will have some intellectual disability or difficulties, but again it is a spectrum. Neuropsychological testing is recommended to define exactly where the strengths are (e.g. memory) and difficulties (e.g. maths). Some people living with FXS will be non-speaking, others will speak several languages. It is also possible that someone may be ‘mosaic’, where the FMR1 gene is fully functioning in some cells and not others. It is important to evaluate each person in light of the complexity of FXS. More information is available in the ‘Genetics’ section.

Further testing on the various physical, behavioural and cognitive aspects (including a range of neuropsychiatric testing) can be ordered by health professionals as appropriate.

Physical Symptoms

Physical symptoms will vary from person to person, but below are those commonly associated with Fragile X Syndrome (FXS).

  • Difficulties sucking/breastfeeding in newborns
  • Excess saliva production
  • Reflusso gastrico
  • Low muscle tone (also known as ‘muscular hypotonia’)
  • Ipermobilità articolare
  • Ear infections in early childhood (also known as ‘otitis media’)
  • Difficulties with balance
  • Large, prominent ears
  • Elongated face (which often occurs during adolescence)
  • Enlarged testicles in males, particularly after puberty (also known as ‘macroorchidism’)
  • Only one crease across the palm of the hand (also known as ‘single transverse palmar crease’)
  • Epileptic seizures which usually stop during puberty (affects 10-25% of males and less than 8% of females)
  • Less common: Mitral valve prolapse (where the valve between the left chambers of the heart does not work properly sometimes causing blood to flow backwards)
  • Fine and gross motor coordination difficulties (more info in the section on ‘Physical Therapy’)

Some of these symptoms are features of FXS and do not require therapies or interventions. Symptoms like low muscle tone, gastric reflux, epilepsy, and mitral valve prolapse should be discussed with a doctor who may put support in place to manage these symptoms.

Emotional Symptoms

As FXS is a spectrum, any individual may have one or more of these symptoms. It is important to get professional support and diagnosis.

More information on symptoms and management are in the ‘Sensory‘ and ‘Behaviour and Therapies‘ sections.

Behavioural Symptoms

As with all rare conditions behavioural symptoms will vary from person to person, but below are the behavioural symptoms commonly associated with Fragile X Syndrome (FXS).

  • Hyperactivity (may be linked to an ADHD diagnosis)
  • Self-stimulatory behaviour (often shortened to stimming) to help self-regulate, including:
    • Hand flapping
    • Mordere le mani
    • Chewing
    • Playing with water
    • Playing with switches
    • Spinning objects
    • And more – these are some examples but this list is not exhaustive
  • Food bolting (eating very quickly, sometimes hardly chewing)
  • Avoiding eye contact
  • Behaviours commonly associated with autism (autism occurs in around ⅓ of individuals with FXS)
  • Sleeping issues (such as early morning waking)
  • Inability to foresee dangerous situations
  • Disinterest in their environment

Many of these symptoms can be managed and improved through behavioural therapies, more information on these is available in the ‘Behaviour and Therapies’ section.

Cognition

One of the main non-physical symptoms of Fragile X Syndrome (FXS) is altered levels of intellect. Levels of intellect vary from person to person, however the majority of people with FXS will have some degree of intellectual disability. Men with FXS often have a lower general IQ than women with FXS, as explained by genetics, however FXS is a spectrum which varies from person to person. The main identifying features of an intellectual disability are delayed development of speech and language, reduced executive function, slower learning and memory/sequencing struggles.

Neuropsychiatric testing is recommended to determine the areas of strength and where help is needed. Verbal and non-verbal IQ tests are available, depending on the person being tested, and the specialist can determine the specific areas of IQ strengths and differences. The individual with FXS may have higher abilities in one area (for example, memory) and need more support in another area (for example, mathematics). Testing can be delivered by neuropsychologists in clinical settings or by educational psychologists in schools.

Today, in addition to traditional IQ tests, there are also tests in Emotional Quotient (EQ) and Social Quotient (SQ). These tests can give a broader picture of strengths and areas needing support. Understanding a person’s strengths helps in teaching skills, developing independence, self-esteem and connection with others. Please see the section on ‘The Strengths of FXS‘.

Further information on supporting someone with FXS can be found in the sections ‘Helping Someone with FXS’ and ‘Terapie non mediche per la sindrome dell'X fragile’.

Recognising Pain

People with Fragile X Syndrome (FXS) may not always be able to communicate the pain they feel. For people with communication difficulties pain may be expressed through comportamento such as irritability or more frequent outbursts. Changes in behaviour can often signal pain, therefore checking up on someone may help them express their pain. The use of a pain scale or a diagram of a body may help an individual communicate whether they are in pain and where they are in pain.

Additionally, people with FXS often have a higher pain tolerance than others, meaning they may not recognise issues within their body. Regular check ups or annual review with medical professionals can help to prevent and treat any issues which may arise. Families have highlighted the importance of regular dental checks, as tooth pain may not be reported and tooth decay not treated.

Further information on helping children with pain is available, including a downloadable resource and the FLACC Pain Scale.

Lifelong Condition

Fragile X Syndrome (FXS) is a lifelong condition with an average life expectancy. As FXS has a range of symptoms, including communication difficulties, individuals will continue to need support into adulthood and beyond. Some people with FXS will be able to live independently, while others may need higher levels of support. This will vary person to person based on individual needs and should be reevaluated as the person grows from childhood into adulthood and further on as they become an older person. More information about this can be found in the section ‘Aiutare una persona con la sindrome dell'X fragile’.

While there is no cure for Fragile X Syndrome there are therapies available for symptom management. FraXI is a charity supporting people living with FXS and their full inclusion in society, rather than focussing on a cure. Current early stage pre-human research into ‘curing’ FXS includes “gene scissoring” CRISPR/Cas, however this has not had success so far due to the complex nature of the FMR1 protein. Other scientists are looking at mRNA therapies, gene activation and FMRP production. More information on current research is available in the ‘Ricerca’ section of the website.

References

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