https://orcid.org/0000-0001-5029-8448
Abstract
The fragile X premutation is characterized by 55–200 CGG repeats in the 5ʹ untranslated region of FMR1, whereas full fragile X mutation has greater than 200 repeats and full methylation, which manifests as fragile X syndrome (FXS). The premutation spectrum of clinical involvement includes fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND). In addition, premutation carriers also suffer from various other health problems such as endocrine abnormalities and autoimmune problems. In this paper, we have discussed different health issues faced by the carriers and interventions including medications, therapy and lifestyle changes that could improve their health.
Summary
An effective management plan required for improving the health of the premutation patients must follow a holistic approach including a thorough screening of psychiatric problems as documented in FXAND. Patients should be educated about various existing medical treatment options in addition to various behavioral interventions such as CBT and numerous biofeedback techniques. Moreover, patients should also be made aware of the importance of physical activity, meditation techniques and the beneficial effects of various antioxidants in slowing the progression of premutation disorders. Careful family history may help carriers understand the diseases that run in the family. When there is a strong family history of FXTAS or FXPOI then the chances that these problems will eventually occur in other carriers in the family are high. The education of all family members regarding the molecular effects of the premutation, the importance of the CGG repeat number and the influence of AGG interruptions and background genetic effects should be carried out so that lifestyle decisions can be made early in adult life.
Acknowledgments
We thank Abijeet Singh Mehta for helping with endnote and proof reading. This study was funded by NICHD HD036071, the Tides Foundation, the MIND Institute IDDRC (grant U54 HD079125), and the National Center for Advancing Translational Sciences and National Institutes of Health (grant UL1 TR001860).
Disclosure
Dr Randi Hagerman reports grants from NICHD, during the conduct of the study; has received funding from Zynerba and the Azrieli Foundation for treatment studies in FXS. The authors report no other conflicts of interest in this work.