Abstract
This chapter offers a synopsis of research studies identifying various sleep patterns in children with Fragile X syndrome. New research has begun to recognize sleep problems across the life span in individuals with Fragile X-associated disorders. Epidemiologic and treatment approaches involve recognizing the interaction of biopsychosocial variables which have been conceptualized using the International Classification of Functioning, Disability and Health-Children and Youth Version. There is a need for well-designed double-blind crossover studies investigating the effectiveness of medications and behavioral interventions in treating sleep problems. The immediate and long-term impact of these treatments on family satisfaction and functioning must also be measured and documented.
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References
Chonchaiya W, Schneider A, Hagerman RJ. Fragile X: a family of disorders. Adv Pediatr. 2009;56(1):165–86.
Hessl D, Rivera SM, Reiss AL. The neuroanatomy and neuroendocrinology of fragile X syndrome. Ment Retard Dev Disabil Res Rev. 2004;10(1):17–24.
Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL, Warren ST. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet. 2009;85(4):503–14.
Bailey DB, Raspa M, Olmsted M, Holiday DB. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am J Med Genet A. 2008;146(16):2060–9.
Monaghan KG, Lyon E, Spector EB. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the standards and guidelines for clinical genetics Laboratories of the American College of medical genetics and genomics. Genet Med. 2013;15(7):575–86.
Dombrowski C, Levesque S, Morel M, Rouillard P, Morgan K, Rousseau F. Premutation and intermediate-size FMR1 alleles in 10 572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet. 2002;11(4):371–8.
Pesso R, Berkenstadt M, Cuckle H, Gak E, Peleg L, Frydman M, Barkai G. Screening for fragile X syndrome in women of reproductive age. Prenat Diagn. 2000;20(8):611–4.
Rousseau F, Rouillard P, Morel M-L, Khandjian EW, Morgan K. Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome. Am J Hum Genet. 1995;57(5):1006.
Tzeng CC, Tsai LP, Hwu WL, Lin SJ, et al. Prevalence of the FMR1 mutation in Taiwan assessed by large-scale screening of newborn boys and analysis of DXS548-FRAXAC1 haplotype. Am J Med Genet A. 2005;133(1):37–43.
Fernandez-Carvajal I, Posadas BL, Pan R, Raske C, Hagerman PJ, Tassone F. Expansion of an FMR1 grey-zone allele to a full mutation in two generations. J Mol Diagn. 2009;11(4):306–10.
Jacquemont S, Hagerman RJ, Leehey MA, Hall DA, et al. Penetrance of the fragile X–associated tremor/ataxia syndrome in a premutation carrier population. JAMA. 2004;291(4):460–9.
Coffey SM, Cook K, Tartaglia N, Tassone F, et al. Expanded clinical phenotype of women with the FMR1 premutation. Am J Med Genet A. 2008;146(8):1009–16.
Hagerman RJ, Hall DA, Coffey S, Leehey M, et al. Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin Interv Aging. 2008;3(2):251.
Jacquemont S, Hagerman RJ, Leehey M, Grigsby J, et al. Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am J Hum Genet. 2003;72(4):869–78.
Hamlin A, Liu Y, Nguyen DV, Tassone F, Zhang L, Hagerman RJ. Sleep apnea in fragile X premutation carriers with and without FXTAS. Am J Med Genet B Neuropsychiatr Genet. 2011;156(8):923–8.
Summers S, Cogswell J, Goodrich J, Mu Y, Nguyen D, Brass S, Hagerman R. Prevalence of restless legs syndrome and sleep quality in carriers of the fragile X premutation. Clin Genet. 2014;86(2):181–4.
Sullivan SD, Welt C, Sherman S. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med. 2011; 29(4):299–307.
Cronister A, Teicher J, Rohlfs EM, Donnenfeld A, Hallam S. Prevalence and instability of fragile X alleles: implications for offering fragile X prenatal diagnosis. Obstet Gynecol. 2008;111(3):596–601.
Seltzer MM, Baker MW, Hong J, Maenner M, Greenberg J, Mandel D. Prevalence of CGG expansions of the FMR1 gene in a US population-based sample. Am J Med Genet B Neuropsychiatr Genet. 2012;159(5):589–97.
Tassone F, Iong KP, Tong T-H, Lo J, et al. FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States. Genome Med. 2012;4(12):100.
Nolin SL, Sah S, Glicksman A, Sherman SL, et al. Fragile X AGG analysis provides new risk predictions for 45–69 repeat alleles. Am J Med Genet A. 2013;161(4):771–8.
Yrigollen CM, Durbin-Johnson B, Gane L, Nelson DL, Hagerman R, Hagerman PJ, Tassone F. AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genet Med. 2012;14(8):729–36.
Hall DA, Berry-Kravis E, Zhang W, Tassone F, et al. FMR1 gray-zone alleles: association with Parkinson’s disease in women? Mov Disord. 2011;26(10):1900–6.
Loesch D, Tassone F, Lo J, Slater H, et al. New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson’s disease. Clin Genet. 2013;84(4):382–5.
Hall D, Tassone F, Klepitskaya O, Leehey M. Fragile X–associated tremor ataxia syndrome in FMR1 gray zone allele carriers. Mov Disord. 2012;27(2):297–301.
Liu Y, Winarni T, Zhang L, Tassone F, Hagerman R. Fragile X-associated tremor/ataxia syndrome (FXTAS) in grey zone carriers. Clin Genet. 2013;84(1):74–7.
Bretherick KL, Fluker MR, Robinson WP. FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure. Hum Genet. 2005;117(4):376–82.
Renda MM, Voigt RG, Babovic-Vuksanovic D, Highsmith WE, Vinson SS, Sadowski CM, Hagerman RJ. Neurodevelopmental disabilities in children with intermediate and premutation range fragile X cytosine-guanine-guanine expansions. J Child Neurol. 2014;29(3):326–30.
Bechara EG, Didiot MC, Melko M, Davidovic L, et al. A novel function for fragile X mental retardation protein in translational activation. PLoS Biol. 2009;7(1):133.
Bushey D, Tononi G, Cirelli C. The Drosophila fragile X mental retardation gene regulates sleep need. J Neurosci. 2009;29(7):1948–61.
Bushey D, Tononi G, Cirelli C. Sleep and synaptic homeostasis: structural evidence in Drosophila. Science. 2011;332(6037):1576–81.
van Alphen B, Yap MH, Kirszenblat L, Kottler B, van Swinderen B. A dynamic deep sleep stage in Drosophila. J Neurosci. 2013;33(16):6917–27.
Tirosh E, Borochowitz Z. Sleep apnea in fragile X syndrome. Am J Med Genet. 1992;43(1–2):124–7.
Ferri R, Del Gracco S, Elia M, Musumeci SA, Pettinato S. Heart rate variability and autonomic function during sleep in fragile X syndrome. Am J Med Genet. 1999;83(4):296–7.
Gould EL, Loesch DZ, Martin MJ, Hagerman RJ, Armstrong SM, Huggins RM. Melatonin profiles and sleep characteristics in boys with fragile X syndrome: a preliminary study. Am J Med Genet. 2000;95(4):307–15.
Miano S, Bruni O, Elia M, Scifo L, et al. Sleep phenotypes of intellectual disability: a polysomnographic evaluation in subjects with Down syndrome and fragile-X syndrome. Clin Neurophysiol. 2008;119(6):1242–7.
Wirojanan J, Jacquemont S, Diaz R, Bacalman S, Anders TF, Hagerman RJ, Goodlin-Jones BL. The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med. 2009;5(2):145.
Kronk R, Dahl R, Noll R. Caregiver reports of sleep problems on a convenience sample of children with fragile X syndrome. Am J Intellect Dev Disabil. 2009;114(6):383–92.
Kronk R, Bishop EE, Raspa M, Bickel JO, Mandel DA, Bailey DB Jr. Prevalence, nature, and correlates of sleep problems among children with fragile X syndrome based on a large scale parent survey. Sleep. 2010;33(5):679.
Symons FJ, Byiers BJ, Raspa M, Bishop E, Bailey DB Jr. Self-injurious behavior and fragile X syndrome: findings from the national fragile X survey. Am J Intellect Dev Disabil. 2010;115(6):473–81.
Chervin RD, Archbold KH, Panahi P, Pituch KJ. Sleep problems seldom addressed at two general pediatric clinics. Pediatrics. 2001;107(6):1375–80.
Mindell JA, Owens JA. Sleep problems in pediatric practice: clinical issues for the pediatric nurse practitioner. J Pediatr Health Care. 2003;17(6):324–31.
Owens JA. The practice of pediatric sleep medicine: results of a community survey. Pediatrics. 2001;108(3):e51.
Lewandowski AS, Toliver-Sokol M, Palermo TM. Evidence-based review of subjective pediatric sleep measures. J Pediatr Psychol. 2011;36(7):780–93.
Kidd SA, Lachiewicz A, Barbouth D, Blitz RK, et al. Fragile X syndrome: a review of associated medical problems. Pediatrics. 2014;134(5):995–1005.
Owens JA, Spirito A, McGuinn M. The Children’s Sleep Habits Questionnaire (CSHQ): psychometric properties of a survey instrument for school-aged children. Sleep. 2000;15(23):1043–51.
Goldman SE, Richdale AL, Clemons T, Malow BA. Parental sleep concerns in autism spectrum disorders: variations from childhood to adolescence. J Autism Dev Disord. 2012;42(4):531–8.
Souders MC, Mason TB, Valladares O, Bucan M, et al. Sleep behaviors and sleep quality in children with autism spectrum disorders. Sleep. 2009;32(12):1566.
Gruber R, Fontil L, Bergmame L, Wiebe ST, Amsel R, Frenette S, Carrier J. Contributions of circadian tendencies and behavioral problems to sleep onset problems of children with ADHD. BMC Psychiatry. 2012;12(1):212.
Sciberras E, Fulton M, Efron D, Oberklaid F, Hiscock H. Managing sleep problems in school aged children with ADHD: a pilot randomised controlled trial. Sleep Med. 2011;12(9):932–5.
Lara Ledesma D. A Spanish version of the Children’s Sleep Habits Questionnaire (CSHQ). Electronic Theses, Projects, and Dissertations 2014;Paper 89. http://scholarworks.lib.csusb.edu/etd/89.
Liu X, Liu L, Owens JA, Kaplan DL. Sleep patterns and sleep problems among schoolchildren in the United States and China. Pediatrics. 2005;115(Suppl 1):241–9.
Tzchishinsky O, Lufi D, Shochat T. Reliability of the Children’s Sleep Habits Questionnaire Hebrew translation and cross cultural comparison of the psychometric properties. Sleep Diagn Ther. 2008;3:30–4.
Sadeh A. Commentary: comparing actigraphy and parental report as measures of children’s sleep. J Pediatr Psychol. 2008;33(4):406–7.
World Health Organization. International classification of functioning, disability, and health: children & youth version: ICF-CY. World Health Organization; 2007.
Mindell JA, Owens JA. A clinical guide to pediatric sleep: diagnosis and management of sleep problems. Philadelphia, PA: Lippincott Williams & Wilkins; 2015.
Weiskop S, Richdale A, Matthews J. Behavioural treatment to reduce sleep problems in children with autism or fragile X syndrome. Dev Med Child Neurol. 2005;47(02):94–104.
Kulman G, Lissoni P, Rovelli F, Roselli MG, Brivio F, Sequeri P. Evidence of pineal endocrine hypofunction in autistic children. Neuroendocrinol Lett. 2000;21(1):31–4.
Tordjman S, Anderson GM, Pichard N, Charbuy H, Touitou Y. Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biol Psychiatry. 2005;57(2):134–8.
Tordjman S, Anderson GM, Bellissant E, Botbol M, et al. Day and nighttime excretion of 6-sulphatoxymelatonin in adolescents and young adults with autistic disorder. Psychoneuroendocrinology. 2012;37(12):1990–7.
Bailey DB, Raspa M, Bishop E, Olmstead M, Mallya U, Berry-Kravis E. Medication utilization for targeted symptoms in children and adults with fragile X syndrome: US survey. J Dev Behav Pediatr. 2012;33:62–9.
Angriman M, Caravale B, Novelli L, Ferri R, Bruni O. Sleep in children with neurodevelopmental disabilities. Neuropediatrics. 2015;46(3):199–210.
Hollway JA, Aman MG. Pharmacological treatment of sleep disturbance in developmental disabilities: a review of the literature. Res Dev Disabil. 2011;32(3):939–62.
Appleton R, Jones AP, Gamble C, Williamson PR, et al. The use of melatonin in children with neurodevelopmental disorders and impaired sleep: a randomized, double-blind, placebo-controlled, parallel study (MENDS). Health Technol Assess. 2012;16(40):8–239.
Hagerman R, Riddle J, Roberts L, Breese K, Fulton M. Survey of the efficacy of clonidine in fragile X syndrome. Dev Brain Dysfunct. 1995;8(4–6):336–44.
Ming X, Gordon E, Kang N, Wagner GC. Use of clonidine in children with autism spectrum disorders. Brain Dev. 2008;30(7):454–60.
Raspa M, Bailey DB Jr, Bishop E, Holiday D, Olmsted M. Obesity, food selectivity, and physical activity in individuals with fragile X syndrome. Am J Intellect Dev Disabil. 2010;115(6):482–95.
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Kronk, R., Filipink, R.A. (2019). Fragile X Syndrome. In: Accardo, J. (eds) Sleep in Children with Neurodevelopmental Disabilities. Springer, Cham. https://doi.org/10.1007/978-3-319-98414-8_22
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DOI: https://doi.org/10.1007/978-3-319-98414-8_22
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