What Is Fragile X Syndrome and Some Suggestions for Moving Forward

Thank you to Content Experts, Karen Kelm, MSc, BA, President of the Fragile X Research Foundation of Canada, and Francois Bolduc, MD, FRCPC, PhD, Associate Professor of Pediatric Neurology & Adjunct Associate Professor of Medical Genetics, University of Alberta, who reviewed and contributed to this resource.

Table of Contents

1. What is Fragile X Syndrome
2. Impacts
3. Prevalence
4. Testing and Diagnosis
5. Supports
6. Suggestions for Assisting Individuals
7. Seeking Health Care Support
8. Transition to Adulthood
9. Support to Families
10. Resources
11. References

1 - What is Fragile X Syndrome

Fragile X syndrome is an inherited genetic disorder. Change in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene affects protein production crucial for brain development. The National Institute of Health states that, “Fragile X results from a change or mutation in the FMR1gene, which is found on the X chromosome. The gene normally makes a protein, called FMRP, that is important for creating and maintaining connections between cells in the brain and nervous system. The mutation causes the body to make only a little bit or none of the protein, which often causes the symptoms of Fragile X (Syndrome).”¹

In addition to Fragile X syndrome, the FMR1 gene can impact individuals in other significant ways through related disorders. These conditions highlight the broader influence of the FMR1 gene on health and well-being:

• FXTAS — Fragile X-Associated Tremor/Ataxia Syndrome: typically occurs in males over 50 and results in balance, tremor, and memory problems that increase as the individual ages.²
• FXPOI — Fragile X-Associated Primary Ovarian Insufficiency: typically occurs in females typically over 40 and impacts ovarian function, potentially resulting in infertility and/or early menopause.²

Fragile X syndrome can result in a variety of cognitive and behavioural challenges, medical issues and physical traits,^2,3,4,5 as illustrated below. It is also important to highlight the unique strengths and positive attributes often seen in individuals with Fragile X syndrome.

Currently, there is no cure for Fragile X Syndrome, but research is ongoing, and new learning is emerging. And there are several interventions (pharmacological and other) which can help individuals with Fragile X Syndrome.

2 - Impacts

• Behavioural impacts: While some may experience sensory processing challenges, anxiety, characteristics of autism, ADHD, aggressive behaviours, and sleep difficulties, individuals with Fragile X often display remarkable creativity and strong visual learning skills. They tend to have a friendly and kind disposition, enjoy social interactions, and can form deep emotional connections with others.
• Cognitive impacts: Various impacts can include a range of learning or intellectual disabilities, speech language challenges, and motor delays. Many individuals with Fragile X possess unique problem-solving skills and a keen ability to think ‘outside the box’. They often excel in tasks that require attention to detail and can thrive in structured learning environments tailored to their strengths.
• Medical issues: Some individuals with Fragile X may experience medical issues, such as ear infections, crossed eyes (strabismus), and seizures. Individuals with Fragile X and premutation carriers have also been noted to experience cardiovascular issues. It is important to note that many individuals with Fragile X lead healthy and active lives, with the proper medical and therapeutic support. Early interventions can significantly enhance quality of life.
• Physical features: Various physical features can include large ears, a long face, a large forehead, low muscle tone, connective tissue issues, soft skin, flexible joints (particularly fingers, wrists and elbows), flat feet, high arched palate, and large testicles (called “macroorchidism”) in post-pubertal males. Some physical features associated with Fragile X, such as flexible joints and connective tissue traits, can contribute to exceptional abilities in certain physical activities or artistic endeavours.

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3 - Prevalence

Fragile X Syndrome is reported to be the most common type of inherited intellectual disability. It affects an estimated 1 in 7,000 males and 1 in 11,000 females.³ Sources report that males often are more severely impacted than females.

For more detail about Fragile X syndrome, see information provided by the Cleveland Clinic³ and the National Fragile X Foundation.²

Additionally, there is a recorded webinar with Dr. Elizabeth Berry-Kravis that addresses aging with Fragile X; the first 30 minutes are most relevant to this topic:https://fragilex.org/webinar/aging-in-fragile-x-syndrome/.⁶

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4 - Testing and Diagnosis

Recommendations for Fragile X testing are offered by the Canadian College of Medical Geneticists: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313961/.⁷ However, a reviewer noted that testing procedures are inconsistent across Canada.

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5 - Supports

There are numerous supports and therapies available that can enhance quality of life and help individuals thrive. Therapeutic supports, such as speech therapy, occupational therapy, and behavioural interventions, can nurture potential and improve daily living skills. Additionally, ongoing research is making strides in developing treatments that target the core mechanisms of Fragile X Syndrome, aiming to unlock even greater potential and opportunities for those affected.

The Fragile X Research Foundation of Canada offers the following resource: Where to Get Help⁸

When symptoms are noted, reaching out to the individual’s doctor is important. This can start a process toward assessment and support. Early intervention is important.¹

Learning as much as possible about Fragile X syndrome will not only gain relevant knowledge. It likely also may help in finding resources. Community supports can be sought from within your region and nationally (see Resources section at the end of this review).

Support with life skills may be helpful to the individual with Fragile X syndrome. The Cleveland Clinic suggests guidance in the areas of social activity, sexuality, recreation, education and employment,³ as examples. Also, various healthcare treatments are outlined in: https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome. This resource further strongly advises consultation with the individual’s health care provider in planning care and support.³

Assisting and advocating for an individual with Fragile X syndrome to get the resources they need is important.³ Support is increasingly available from the Fragile X Research Foundation of Canada. This organization has promoted Fragile X research, but also is increasingly advancing supports to Canadian families. For more information, seehttps://www.fragilexcanada.ca/.⁹

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6 - Suggestions for Assisting Individuals

Free online information entitled, An Introduction to ‘Learning and Living the Fragile X Way’ and the Benefits of Care Mapping, is offered by Tracy Murnan Stackhouse, MA, OTR/L and the DFX team at the Fragile X Academy in Denver Colorado.¹⁰ A holistic approach is offered that addresses strengths, supports and needs, with an aim of thriving. Care mapping is described as a means to identify current supports and resources related to the individual, and in turn, help to determine needs for accessing further support. This Care Mapping resource features Karen Kelm, President of the Fragile X Research Foundation of Canada. Note that additional training resources are offered on this site, but there are fees for some resources.

Dr. Jennifer Epstein, a clinical psychologist, offers a resource entitled, Building Social Supports: A Guide for Parents¹¹, at: https://fragilex.org/fxs/daily-living/building-social-supports-a-guide-for-parents. She notes that individuals with Fragile X syndrome often experience challenges with meaningful friendships. Challenges that may affect friendships may include difficulties with social skills, social anxiety, and distinct areas of interest. Dr. Epstein proposes the following strategies to help address challenges that an individual with Fragile X syndrome may encounter:¹¹

1. Share information and advocate: Many people may not have knowledge about Fragile X syndrome or how to engage constructively with an individual with Fragile X syndrome. Letting others know what the individual wants and needs may be helpful in potentially creating spaces for them to be included in ways that are supportive. Dr. Epstein addresses the potential to help with friendships and social skills. But she also indicates the need to be careful to limit social anxiety, find areas of common interest, and limit unhelpful sensory stimulation and social demands.
2. Support skills such as social skills early on: Look for opportunities to support engagement in play for a child with Fragile X syndrome. Play can be a helpful way to learn and practice social skills. Specific skills can include things like beginning conversations, turn taking, inquiring, and sharing ideas with others. This can begin in conversations with siblings or other family members. Then with practice, these skills can be moved beyond the home. Finding others in the community who are supportive in these conversations and social skill development activities, may be helpful.
3. Individualized supports: Meeting with a professional to work on key areas of skill development or address challenges can be helpful. For instance, a professional could support the development of social skills. It is important to find a support professional with an understanding of Fragile X. They may offer greater insight in terms of addressing key challenges, and understanding what may underlie these challenges and what may help in moving forward.
4. Tangible and visual cues and supports: Concrete tools such as visual cues and pictures may be helpful for some people. This helps to make abstract or broad ideas clearer and more concrete. For tracking conversations or remembering information, visual cues or reminders may be helpful. Begin to ask what is helpful for the individual. Is writing or drawing ideas helpful in focusing attention or remembering what has been said? As an example, drawing (even in a simple way) a social encounter could help address approaches to engage and work on social skills.
5. Social scripting: This is an approach that offers ways to deal with challenges in social relationships, but also supports anxiety that may go with these challenges. If someone feels overwhelmed particularly in social interactions, it may be difficult to engage in conversation. Social scripting is a tool to help someone start a conversation, and respond to questions or comments. This may involve practicing these communicative steps, and could be done by the individual and a family member or another support person. Dr. Epstein cautions that given how different each of us are, approaches such as social scripting need to be tried to see what works or possibly doesn’t work. And if something isn’t working, the approach can be modified.
6. Facilitated support with social interaction: Some people with Fragile X syndrome may benefit from supportive social relationships. Setting up social relationships in a good way may be important for moving forward well. One strategy that someone might use is called “supportive scaffolding”. That involves ensuring enough structure in the communication or process of engagement to help increase predictability. Knowing better what will happen (e.g., activities, having a snack break, timeline, etc.) may help bring structure and a sense of security to the social exchange that otherwise might seem too difficult, confusing or uncertain. Keeping social engagements shorter, at least initially, might make them less overwhelming.

Supporting social engagement and exchanges may be helpful. This could include introductions, taking turns, and structured sharing in play. Also having activities that are structured may be helpful. Examples include activity such as going to, or playing, a sporting activity (e.g., bowling) in which there are clear rules and structure to the social encounter.

As noted, these suggestions are offered by Dr. Epstein’s resource¹¹ at: https://fragilex.org/fxs/daily-living/building-social-supports-a-guide-for-parents. Please consult this resource for further detail.

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7 - Seeking Health Care Support

A Canadian toolkit to support an individual or family gain access to health care support was developed by the Health Care Access Research and Developmental Disabilities (H-CARDD) program and Vita Community Living Services (CLS).¹² The toolkit can be found at:https://nutsandbolts.ddtoolkits.com. This resource addresses a range of intellectual and developmental disabilities, including Fragile X syndrome.

It is important to note that multiple resources in other intellectual and developmental disabilities may be beneficial in supporting individuals with Fragile X syndrome. Such resources on the AIDE Canada website and elsewhere may be helpful, such as: Resources Supporting Health Care for Individuals with Intellectual and Developmental Disabilities

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8 - Transition to Adulthood

Generally, individuals with Fragile X syndrome have a typical life expectancy, and thus it is important to prepare for, and ensure support in, their transition to and through adulthood. The Fragile X Research Foundation of Canada¹³ notes that there is not a specific Canadian program that takes over after a child completes high school, and suggests that individuals and/or families reach out to their local Community Living service to connect about resources. The Fragile X Research Foundation of Canada outlines several key areas for consideration in the transition to adulthood:¹³

• Transportation – While some individuals learn to drive, many are reliant on public transportation and may need to learn how to navigate these systems.
• Vocational training to succeed in the workplace is important. This support ideally begins in high school, with the help of local service agencies.
• Financial planning for parents/families around the long-term needs of the individual with Fragile X Syndrome is important. A Registered Disability Savings Plan (RDSP) is one potential resource in Canada, and there other resources that may be particular to provinces and territories. For more description about the RDSP, an infosheet¹⁴ is found on the AIDE Canada website at: https://aidecanada.ca/resources/learn/asd-id-core-knowledge/infosheet---rdsp---pooranlaw. Further financial resource information likely is available from provincial/territorial government disability offices.
• Housing – There are often long waitlists due to shortages in residential services, so early planning for future living situations as an adult is key. There is a range of different supportive housing options depending on the support needs of the individual and the community that they live in. Connecting early with service providers to discuss future housing plans is suggested. As an example of further information about housing, see AIDE Canada’s toolkit on housing¹⁵:

Helpful interventions and supports for adults with Fragile X include the following:

• Medication may be helpful with challenging or associated issues, but other non-pharmacological supports may be important for substantial advances,
• Community engagement and inclusion,
• Support for community and social engagement, and
• Support in terms of social behavior.⁶

Other priorities to address include:

• Finding health care and community support providers as individuals move into and through adulthood,
• Ensuring guardianship and trusteeship is in place prior to transitioning to adulthood, as required, and
• More research to better understand the needs of, and resources that are helpful for, adults with Fragile X Syndrome.

An informative guide addressing transition to adulthood is entitled, Transition to Adult Services for Individuals with Fragile X Syndrome.¹⁶ Key areas to consider are offered: https://fragilex.org/wp-content/uploads/Adult-Services-Consensus-Document.pdf.

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9 - Support to Families

Reviewer Karen Kelm noted, “Due to the unique inheritance pattern of Fragile X syndrome, it is crucial to consider the broader familial context when supporting an individual with this condition. Fragile X syndrome is often passed down from a parent, typically the mother, who may also be affected by the syndrome or be a carrier of the FMR1 gene mutation. This means that while providing support, it is essential to acknowledge and address the potential challenges the parent might be facing as well. Understanding and supporting both the individual and their family can lead to more comprehensive and effective care, recognizing that the emotional and physical well-being of the caregiver is integral to the overall support system.”

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10 - Resources

Below are some resources offering information and/or support related to Fragile X Syndrome.

• Fragile X Research Foundation of Canada website; also see the Where to Get Help site.
• Fragile X Academy (information offered, but some with costs). Includes information and resources based locally in the USA. Please be advised that some resources require payment.

   

  Note that free online information is offered entitled, An Introduction to ‘Learning and Living the Fragile X Way’ and the Benefits of Care Mapping by Tracy Murnan Stackhouse, MA, OTR/L and the DFX team at the Fragile X Academy in Denver Colorado: https://dfxlearningjourneys.thinkific.com/courses/FX-Overview-and-Care-Mapping.

  A holistic approach is offered that addresses strengths, supports and needs of an individual, with the aim of supporting them in thriving. Care mapping is described as a way of holistically identifying supports and resources. The Care Mapping session by Tracy Murnan Stackhouse features Karen Kelm of the Fragile X Research Foundation of Canada.

  Additional resources from this source can be found at:
  • https://developmentalfx.org/fragile-x-academy/
  • https://developmentalfx.org/resources-for-parents-2/
  
  
• Fragile X information from Marcia Braden, PhD., P.C. This site offers some free information, and also references resources that require payment: https://www.marciabraden.com
• Fragile X Syndrome. Cleveland Clinic: A helpful resource offered by the Cleveland Clinic: https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome
• National Fragile X Foundation is an American website which includes resources like:
  • Resources for Families
  • Building Social Supports
  • Fragile X Syndrome Resources by Age Group
• Health Supervision for Children with Fragile X Syndrome (AAP Policy Statement) Hersh, J.H., Saul, R.A, & Committee on Genetics (2011). Pediatrics, 127 (5): 994–1006. https://doi.org/10.1542/peds.2010-3500
• The Nuts and Bolts of Health Care for Direct Support Professionals Toolkit: https://nutsandbolts.ddtoolkits.com/ by Perry, A., Hingsburger, D., Malhas, M., Orr, E., Zaretsky, L., Hermans, H., Salonia, C., Selick, A., Volpe, T., & Lunsky, Y. (2019). Toronto, ON: Health Care Access Research and Developmental Disabilities Program.
• Transition to Adult Services for Individuals with Fragile X Syndrome: https://fragilex.org/wp-content/uploads/Adult-Services-Consensus-Document.pdf: Braden, M., Cohen, J., Lang, M., Lang,T., Levitas, A., Turk, J., Jayne Dixon Weber, J & members of the Fragile X Clinical & Research Consortium, National Fragile X Foundation (2020).
• Research information related to Fragile X: https://www.fraxa.org/
• US Department of Health and Human Services: What Causes Fragile X Syndrome? https://www.nichd.nih.gov/health/topics/fragilex/conditioninfo/causes

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11 - References

1. US Department of Health and Human Services: What Causes Fragile X Syndrome?:  https://www.nichd.nih.gov/health/topics/fragilex/conditioninfo/causes , accessed 15 July 2024.
2. National Fragile X Foundation. Fragile X 101. https://fragilex.org/understanding-fragile-x/fragile-x-101/: accessed 9 June 2024.
3. Fragile X Syndrome (FXS). https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome: accessed 9 June 2024.
4. Hagerman, P. J., & Hagerman, R. (2021). Fragile X syndrome. Current Biology, 31(6), PR273-PR275. https://doi.org/10.1016/j.cub.2021.01.043
5. Tassanakijpanich, N., Cohen, J., Cohen, R., Srivatsa, U. N., & Hagerman, R. J. (2020). Cardiovascular problems in the Fragile X premutation. Frontiers in Genetics, 11, 1-8. https://doi.org/10.3389/fgene.2020.586910
6. Berry-Kravis, E. Adult Issues and Aging in FXS (Webinar). What Weʼve Learned from FORWARD About Aging in Fragile X Syndrome — National Fragile X Foundation Webinar. https://fragilex.org/webinar/aging-in-fragile-x-syndrome/
7. Carter MT, Srour M, Au PB, Buhas D, Dyack S, Eaton A, Inbar-Feigenberg M, Howley H, Kawamura A, Lewis SME, McCready E, Nelson TN, Vallance H; Canadian College of Medical Geneticists. Genetic and metabolic investigations for neurodevelopmental disorders: Position statement of the Canadian College of Medical Geneticists (CCMG). J Med Genet. 2023 Jun;60(6):523-532. doi: 10.1136/jmg-2022-108962. Epub 2023 Feb 23. PMID: 36822643; PMCID: PMC10313961.
8. Where to Get Help. https://www.fragilexcanada.ca/newly-diagnosed/where-to-get-help/, accessed 17 July 2024.
9. Fragile X Research Foundation of Canada. https://www.fragilexcanada.ca/, accessed 17 July 2024.
10. Murnan Stackhouse, T. and the DFX team, An Introduction to ‘Learning and Living the Fragile X Way’ and the Benefits of Care Mapping. Fragile X Academy, Denver Colorado: https://dfxlearningjourneys.thinkific.com/courses/FX-Overview-and-Care-Mapping : accessed 9 July 2024.
11. Epstein, J., Building Social Supports: A Guide for Parents. In National Fragile X Foundation. https://fragilex.org/fxs/daily-living/building-social-supports-a-guide-for-parents/: accessed 9 June 2024.
12. Perry, A., Hingsburger, D., Malhas, M., Orr, E., Zaretsky, L., Hermans, H., Salonia, C., Selick, A., Volpe, T., & Lunsky, Y. (2019). The Nuts and Bolts of Health Care for Direct Support Professionals Toolkit. Toronto, ON: Health Care Access Research and Developmental Disabilities Program. https://nutsandbolts.ddtoolkits.com/docs/Nuts%20and%20Bolts_FullToolkit.pdf: accessed 9 June 2024.
13. Fragile X Research Foundation of Canada. Adulthood 21+ Years.https://www.fragilexcanada.ca/living-with-fragile-x-syndrome/adulthood-21-years : accessed 9 June 2024.
14. AIDE Canada. Registered Disability Savings Plan (RDSP) Infosheet.
15. https://aidecanada.ca/resources/learn/asd-id-core-knowledge/infosheet---rdsp---pooranlaw; ACCESSED 27 July 2024.
16. AIDE Canada. Enjoying My Home: Supported Housing Options for Autism and Intellectual Disability in Canada.  https://aidecanada.ca/resources/learn/housing/enjoying-my-home-supported-housing-considerations-and-options-in-autism-and-intellectual-disability : accessed 9 June 2024.
17. Braden, M., Cohen, J., Lang, M., Lang,T., Levitas, A., Turk, J., Jayne Dixon Weber, J & members of the Fragile X Clinical & Research Consortium, National Fragile X Foundation (2020). Transition to Adult Services for Individuals with Fragile X Syndrome. https://fragilex.org/wp-content/uploads/Adult-Services-Consensus-Document.pdf: accessed 9 June 2024.

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