Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;188(4):1029-1039.
doi: 10.1002/ajmg.a.62601. Epub 2021 Dec 10.

Sleep problems in fragile X syndrome: Cross-sectional analysis of a large clinic-based cohort

Dejan B Budimirovic  1   2 , Dragana D Protic  3 , Carol M Delahunty  4 , Howard F Andrews  5   6 , Tse-Hwei Choo  6 , Qing Xu  6 , Elizabeth Berry-Kravis  7   8   9 , Walter E Kaufmann  10   11 ; FORWARD Consortium
Affiliations

Sleep problems in fragile X syndrome: Cross-sectional analysis of a large clinic-based cohort

Dejan B Budimirovic et al. Am J Med Genet A. 2022 Apr.

Abstract

Fragile X syndrome (FXS), the leading cause of inherited intellectual disability and autism spectrum disorder, is associated with multiple neurobehavioral abnormalities including sleep difficulties. Nonetheless, frequency, severity, and consequences of sleep problems are still unclear. The Fragile X Online Registry with Accessible Research Database (FORWARD-version-3), including Clinician Report and Parent Report forms, was analyzed for frequency, severity, relationship with behavioral problems, and impact of sleep difficulties in a mainly pediatric cohort. A focused evaluation of sleep apnea was also conducted. Six surveyed sleep difficulties were moderately frequent (~23%-46%), relatively mild, affected predominantly younger males, and considered a problem for 7%-20% of families. Snoring was more prevalent in older individuals. All sleep difficulties were associated with irritability/aggression and most also to hyperactivity. Only severe snoring was correlated with sleep apnea (loud snoring: 30%; sleep apnea: 2%-3%). Sleep difficulties are prevalent in children with FXS and, although they tend to be mild, they are associated with behavioral problems and negative impact to families. Because of its cross-sectional nature, clinic-origin, use of ad hoc data collection forms, and lack of treatment data, the present study should be considered foundational for future research aiming at better recognition and management of sleep problems in FXS.

Keywords: fragile X syndrome; insomnia; problem behaviors; quality of life; sleep apnea.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

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; DBB receives no personal funds and the Institute has no relevant financial interest in any of the commercial entities listed. Elizabeth Berry-Kravis has received funding from Acadia, Alcobra, AMO, Asuragen, BioMarin, Cydan, Fulcrum, GeneTx, GW, Ionis, Lumos, Marinus, Neuren, Neurotrope, Novartis, Ovid,Roche, Seaside Therapeutics, Ultragenyx, Vtesse/Sucampo/Mallinckrodt, Yamo, and Zynerba Pharmaceuticals to consult on clinical trial design, run clinical trials, or develop testing standards or biomarkers, all of which is directed to RUMC in support of rare disease programs; E.B.-K. receives no personal funds, and RUMC has no relevant financial interest in any of the commercial entities listed. Walter E. Kaufmann is Chief Medical Officer of Anavex Life Sciences Corp. He has been a consultant to AveXis, EryDel, GW, Marinus, Neuren, Newron, Ovid, Stalicla, and Zynerba. Currently, WEK does not receive personal funds and has no financial interest in any of these commercial entities. The other co-authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Summary of findings. A. Frequency of sleep difficulties and their impact to families. B. Frequency of behavioral abnormalities in each difficulty (Present) group. Abbreviation: OCD- obsessive compulsive disorder
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Agar G, Brown C, Sutherland D, Coulborn S, Oliver C, & Richards C (2021). Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile. Mol Autism, 12(1), 18. doi:10.1186/s13229-021-00426-w - DOI - PMC - PubMed
    1. Astill RG, Van der Heijden KB, Van Ijzendoorn MH, & Van Someren EJ (2012). Sleep, cognition, and behavioral problems in school-age children: a century of research meta-analyzed. Psychol Bull, 138(6), 1109–1138. doi:10.1037/a0028204 - DOI - PubMed
    1. Boudewyns A, Abel F, Alexopoulos E, Evangelisti M, Kaditis A, Miano S, … Verhulst SL (2017). Adenotonsillectomy to treat obstructive sleep apnea: Is it enough? Pediatr Pulmonol, 52(5), 699–709. doi:10.1002/ppul.23641 - DOI - PubMed
    1. Budimirovic B, Haas-Givler B, Blitz R, Esler A, Kaufmann W, Sudhalter V, … Berry-Kravis E (2014. (updated 2020)). Understanding autism spectrum disorders in fragile X syndrome. Retrieved from https://fragilex.org/our-research/treatment-recommendations/understandin...
    1. Budimirovic B, Schlageter A, Filipovic-Sadic S, Protic DD, Bram E, Mahone EM, … Latham GJ (2020). A Genotype-Phenotype Study of High-Resolution FMR1 Nucleic Acid and Protein Analyses in Fragile X Patients with Neurobehavioral Assessments. Brain Sci, 10(10). doi:10.3390/brainsci10100694 - DOI - PMC - PubMed

Publication types