Researchers: Emily Graves Allen, Krista Charen, Heather Hipp, Lisa Shubeck, Ashima Amin, Weiya He, Jessica Ezzell Hunter, and Stephanie Sherman
Drs. Emily Allen, Stephanie Sherman (Emory University), and colleagues evaluated health conditions among women who carry an FMR1 premutation. Two conditions, FXPOI and FXTAS, have been well documented among individuals with a premutation. These authors sought to clarify how often other health-related conditions, such as migraines and sleep problems, occur among women with a premutation.
Participants included 355 women with a premutation ranging from 19 to 93 years of age. Of this group, 87 participants had been previously diagnosed with FXPOI. Participants completed questionnaires about whether they experienced or were diagnosed with health conditions such as anxiety/depression, headaches, FXTAS-associated symptoms, sleep problems, and hypertension, among others.
The most commonly reported conditions were anxiety and depression, as well as migraine and tension headaches. Forty-seven percent of women reported the presence of four or more conditions. Body mass index and smoking were associated with experiencing a higher number of conditions and having a child with Fragile X syndrome was associated with increased rates of anxiety and depression.
The study team also used an approach called a “cluster analysis” to determine whether particular conditions tended to occur together. They found eight sub-groups of participants based on the conditions they reported. The biggest group (123 women) had few reported health problems. Two sub-groups included women who reported headaches or mental health problems, but few other conditions. One sub-group included women with sleep problems who reported several other health conditions. Among the three sub-groups of women who had a high rate of a diagnosis of FXPOI (87 people), different patterns emerged: those with minimal health problems, those with mental health problems, and those with multiple conditions such as chronic muscle pain, fibromyalgia, and/or irritable bowel syndrome. The last sub-group (11 women) had symptoms related to FXTAS (e.g., tremor, ataxia, and neuropathy), but few other conditions.
Why This Matters
This study highlights the variability in health profiles among women with a premutation. The majority of women report few health problems, however a significant group report complex health profiles. This study takes the first step to characterize this variability and to understand the impact of an FMR1 premutation as well as environmental factors, such as body mass index and smoking, that may negatively affect health among women with a premutation.
Researchers would like to better understand why the health profiles are so diverse among women with a premutation — what are the genetic and environmental factors associated protection and risk? How can those be identified to help weaken the effect of a premutation and improve health? Clearly, more work is needed.
Funding: This work was supported by an award (NIH U54NS09185) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke.
more research results
This study is important for later-diagnosed individuals as it creates successful predictive models that can identify cases five years earlier than clinical diagnosis.
Data from 8 unique studies speaks to the necessity of early identification of FXS, which leads to earlier, effective medical and non-medical interventions.
Your summary of the results, including why it matters to you and next steps, from the Dr. Liz Berry-Kravis and Tetra Therapeutics BPN14770 trial results published in Nature Medicine. This was a randomized, double-blind, placebo-controlled, two-period crossover study.
Cortical Gyrification and Its Relationships With Molecular Measures and Cognition in Children With the FMR1 Premutation
Jun Yi Wang and the study team out of the UC Davis MIND Institute are interested in learning more about the premutation carrier condition in relations to brain development and its impact on cognition. These mental processes impact the higher-level functions of the brain including language, learning new things, and making decisions.
Telehealth-Enabled Behavioral Treatment for Problem Behaviors in Boys With Fragile X Syndrome: A Randomized Controlled Trial
Dr. Hall and his team at Stanford University are learning about potential behavioral treatments for problem behaviors. Previous research suggests that problem behaviors, like aggression, self-injury, and property destruction, may occur at higher rates in individuals with FXS.
A Genotype-Phenotype Study of High-Resolution FMR1 Nucleic Acid and Protein Analyses in Fragile X Patients with Neurobehavioral Assessments
We know that FMRP is expressed throughout our body, including our blood, tissues, and brain. Levels of FMRP in the blood of patients with FXS have been positively correlated with cognitive performance, specifically intelligence quotient and adaptive behavior.