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Clinical Manifestation and Management of FXPOI

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FXTAS, FXPOI, and Other Premutation Disorders

Abstract

Fragile X-associated primary ovarian insufficiency (FXPOI) is among a family of disorders caused by the expansion of a CGG repeat sequence located in the 5′ untranslated region of the X-linked gene FMR1. About 20 % of women who carry a premutation have cessation of menses for at least 1 year prior to age 40, a 20-fold increased risk compared with the general population. Further, the frequency of women with the premutation attending reproductive endocrinology clinics for infertility is significantly increased compared with the carrier frequency expected in the general population, ~3 % compared with 1/150–1/250. This makes FXPOI the leading known inherited cause of idiopathic POI. Cross-sectional studies clearly show the health burden related to the clinical outcomes associated with FXPOI. Despite the significant reduction in reproductive life span and increased frequency of estrogen deficiency-related medical conditions among women with the premutation who are diagnosed with FXPOI, little is known about the underlying molecular etiology. In this chapter, we focus on describing the clinical manifestation of FXPOI, the risk factors that potentially lead to earlier onset and severity, and the clinical management that can help ameliorate symptoms.

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Acknowledgements

This work was supported in part by an award (NS091859) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS) (S.L.S., E.G.A., and J.S.) and by the Intramural Research Program, Eunice Kennedy Shriver NICHD, National Institutes of Health (L.M.N.)

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Authors and Affiliations

  1. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA

    Stephanie L. Sherman & Emily G. Allen

  2. Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA

    Jessica B. Spencer

  3. Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Lawrence M. Nelson U.S.P.H.S.

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  1. Stephanie L. Sherman
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  2. Emily G. Allen
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  3. Jessica B. Spencer
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  4. Lawrence M. Nelson U.S.P.H.S.
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Correspondence to Stephanie L. Sherman .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, University of California, Davis, California, USA

    Flora Tassone

  2. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA

    Deborah A. Hall

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Sherman, S.L., Allen, E.G., Spencer, J.B., Nelson, L.M. (2016). Clinical Manifestation and Management of FXPOI. In: Tassone, F., Hall, D. (eds) FXTAS, FXPOI, and Other Premutation Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-33898-9_10

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