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Review
. 2022 Feb 9;23(4):1935.
doi: 10.3390/ijms23041935.

Fragile X Syndrome: From Molecular Aspect to Clinical Treatment

Dragana D Protic  1 , Ramkumar Aishworiya  2   3 , Maria Jimena Salcedo-Arellano  2   4   5 , Si Jie Tang  2 , Jelena Milisavljevic  6 , Filip Mitrovic  6 , Randi J Hagerman  2   4 , Dejan B Budimirovic  7   8
Affiliations
Review

Fragile X Syndrome: From Molecular Aspect to Clinical Treatment

Dragana D Protic et al. Int J Mol Sci. .

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the full mutation as well as highly localized methylation of the fragile X mental retardation 1 (FMR1) gene on the long arm of the X chromosome. Children with FXS are commonly co-diagnosed with Autism Spectrum Disorder, attention and learning problems, anxiety, aggressive behavior and sleep disorder, and early interventions have improved many behavior symptoms associated with FXS. In this review, we performed a literature search of original and review articles data of clinical trials and book chapters using MEDLINE (1990-2021) and ClinicalTrials.gov. While we have reviewed the biological importance of the fragile X mental retardation protein (FMRP), the FXS phenotype, and current diagnosis techniques, the emphasis of this review is on clinical interventions. Early non-pharmacological interventions in combination with pharmacotherapy and targeted treatments aiming to reverse dysregulated brain pathways are the mainstream of treatment in FXS. Overall, early diagnosis and interventions are fundamental to achieve optimal clinical outcomes in FXS.

Keywords: FMR1 gene; FMRP; autism spectrum disorder; behavior problems; fragile X syndrome.

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Conflict of interest statement

Randi J. Hagerman has received funding from the Azrieli Foundation and from Zynerba Pharmaceuticals to carry out treatment studies in FXS. She has also consulted with Zynerba Pharmaceuticals for the development of the fragile X protocol for such studies. Dejan B. Budimirovic has received funding from Seaside, Roche, Neuren, Pfizer, Shire, Lundbeck, Forest, Sunovion, SyneuRX, Alcobra, Akili, Medgenics, Purdue, Supernus as a main sub-investigator, and from Ovid and Zynerba Pharmaceuticals as a principal investigator on clinical trials. He also consulted on clinical trial outcome measures (Seaside, Ovid). All the above funding has been directed to Kennedy Krieger Institute/the Johns Hopkins Medical Institutions; Dejan B. Budimirovic receives no personal funds and the Institute has no relevant financial interest in any of the commercial entities listed. The other co-authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Four brothers with typical physical features of FXS. All four boys have prominent broad foreheads, high palate, joint hypermobility and especially prominent ear pinnae. The family gave consent to publish this picture.
Figure 2
Figure 2
Schematic presentation of non-pharmacological interventions for fragile X syndrome. (Created with BioRender.com, accessed on 18 December 2021).
See this image and copyright information in PMC

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