In 2018 Dr. Randi Hagerman, medical director and developmental paediatrician 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).
The paper is a review focussing on neuropsychiatric disorders experienced by approximately 50% of Fragile X premutation carriers with 55-200 repeats. It noted that neuropsychiatric disorders in children with the premutation include anxiety, ADHD, social deficits, or autism spectrum disorders (ASD). In adults with the premutation, anxiety and depression are the most common problems. The problems experienced are often exacerbated by chronic fatigue, chronic pain, fibromyalgia, autoimmune disorders and sleep problems, which are also associated with the Fragile X premutation.
“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.”
Source of quoted section: National Fragile X Foundation website, June 2019
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.
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?
Download the Fragile X-Associated Neuropsychiatric Disorders (FXAND) paper here.
Cittaion: Fragile X-Associated Neuropsychiatric Disorders (FXAND), Randi J. Hagerman, Dragana Protic, Akash Rajaratnam, Maria J. Salcedo-Arellano, Elber Yuksel Aydin and Andrea Schneider, Frontiers in Psychiatry, 13 November 2018.
To learn more:
Filmed for Fragile X Association of Australia, September 2018. (viewing time: 90 seconds)
Q&A with Dr Randi Hagerman, filmed for Fragile X Association of Australia, September 2018. (viewing time 6 minutes)
Q&A with Dr Randi Hagerman, filmed in for Fragile X Association of Australia, September 2018. (viewing time 7 minutes)
Filmed for Fragile X Association of Australia, 2015. (viewing time 42 mins)
Espinel and Sherman, Emory University, Georgia, USA, 2015.