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.

Next Steps

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.

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