FXAND: What is it and what might it mean to you?
Recently, Dr. Randi Hagerman, medical director and developmental pediatrician at the UC Davis MIND Institute in California, published an article in the scientific journal Frontiers in Psychiatry, titled Fragile X-Associated Neuropsychiatric Disorders (FXAND). Dr. Hagerman is well-known in the worldwide Fragile X community for her pioneering work in Fragile X syndrome (FXS) and Fragile X-associated tremor ataxia syndrome (FXTAS). For many years, she has believed that carriers of a Fragile X premutation are at risk for a variety of mental health and medical problems due to the premutation itself. The above-referenced article is one of the first attempts by Dr. Hagerman to describe what she and her colleagues believe to be the scientific basis for those problems. The paper also proposes the recognition of the diagnostic term “FXAND” in order to “promote research and the use of fragile X DNA testing to enhance recognition and treatment for these disorders.”
Dr. Hagerman and her team describe anxiety, depression, attention deficit hyperactive disorder (ADHD), chronic pain, fibromyalgia, chronic fatigue, sleep disturbances, and autoimmune problems as potentially related to carrying a Fragile X premutation. They suggest that the identified toxic effect of the premutation on the brain may underlie these problems.
It is important to note that the symptoms described in Dr. Hagerman’s article are relatively common in the general population, and many individuals without Fragile X premutations are affected by these same medical and psychological problems. However previous research by her team and others have shown that these symptoms are more common in premutation carriers compared to those who are not carriers. Many carriers of a premutation do not experience any such symptoms while others experience several. Therefore, Dr. Hagerman lists some of the important questions that medical researchers are seeking to understand:
- Are there biomarkers or other genetic changes that can be additive to the premutation that make these symptoms more common?
- Are the described clinical associations due to chance or to higher rates of reporting by carriers compared with non-carriers?
- Are there other possible explanations for the described associations that are not directly related to the premutation itself?
For example, raising a child with Fragile X syndrome (in the case where a premutation carrier has a child or children with the syndrome) can be very stressful, and stress has been associated with a whole host of medical and psychological problems. Being a carrier of a premutation and having an increased risk of Fragile X-associated Primary Ovarian Insufficiency (FXPOI) or FXTAS can also be stress-provoking. We know that environmental stresses can be additive to the premutation propensity to these symptoms. An example of this is how smoking can enhance your risk for FXPOI.
The National Fragile X Foundation (NFXF) thinks that it is important for people who carry a premutation to understand that the paper by Dr. Hagerman is part of the scientific process whereby researchers study an issue, attempt to draw conclusions from their work, and publish their findings in a peer-reviewed journal. This is the first step. Dr. Hagerman and other researchers will continue to ask important questions to better understand the outcomes related to a premutation. Dr. Hagerman feels that unless these neuropsychiatric problems are named, physicians and other health care providers will not recognize them. She added that many carriers feel that they need these problems validated by the health care field and that more research needs to take place regarding the treatment of these problems. The NFXF emphasizes the importance for each carrier to seek help if they are experiencing any health or psychiatric symptoms. There are treatments such as counseling, antidepressants, antianxiety medications, antioxidants and exercise available to reduce symptoms. We also know that having a healthy lifestyle and minimizing stress is always helpful to increase health and quality of life.
Additional resources: The NFXF publishes treatment guidelines for all of the Fragile X-associated disorders.
Dr. Randi Hagerman presented on this topic at the 16th NFXF International Fragile X Conference in July 2018.
In her session, Dr. Hagerman discusses new research in premutation research including:
- MRI changes through the lifespan.
- Occasional occurrences of white matter disease prior to clinical symptoms of FXTAS.
- Clinical correlations of the CGG repeat number and vulnerability of premutation neurons.
- Thoughts about how to stay healthy with the premutation.
- New treatments for FXTAS.
There is also a Q&A with the audience at the end of the presentation.
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