Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile

Abstract

Background Sleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven ‘risk’, inform prognosis and enhance understanding of aetiology of sleep disorders. Method Following PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome. Results Two hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader–Willi, Rett, Smith–Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72–77%), while excessive daytime sleepiness was highest in Smith–Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual’s environment or associated developmental delay, rather than any specific genetic syndromes. Limitations Due to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included. Conclusions Differing prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader–Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed.

Sleep in Children With Pallister Killian Syndrome: A Prospective Clinical and Videopolysomnographic Study

“…The VPSG allowed us to objectively characterize the sleep pattern, significantly altered in PKS children compared with healthy controls. The highest prevalence of SDs reflects what was previously reported about SDs in the main NDDs ( 5 , 6 , 15 ).…”

“…A recent meta-analysis investigated the prevalence of sleep disorders (SDs) in 19 rare genetic syndromes (GSs) and found an average higher frequency than in TD children, with extreme variability in the type of sleep disorder across syndromes ( 6 ).…”

“…Several anatomical, physiological, and neurological factors, typical for the different GSs, may contribute to altering sleep: the altered melatonin secretion leads to circadian rhythm disruption in Smith–Magenis syndrome, while hypotonia determines frequent breathing disorders in Down and Angelman syndrome ( 7 , 8 ). Other frequent causes are poor sleep hygiene, pain caused by co-occurring medical conditions, epilepsy, and adverse effects of drug therapies ( 6 , 9 ). It is important to correctly investigate the pattern of alteration to assess the most appropriate treatment ( 5 ).…”

Sleep, Behavior, and Adaptive Function in KAT6A Syndrome

“…This prevalence of general sleep issues is more similar to disorders with a known disrupted sleep component such as Angelman syndrome or Rett syndrome than other genetic syndromes causing intellectual disability such as Fragile X or Down syndrome or Tuberous Sclerosis Complex [29]. Rates of snoring and apnea were similar to many other genetic syndromes such as Fragile X syndrome and Rett syndrome and lower than others such as Down syndrome and Prader-Willi syndrome [29]. Apnea and snoring only accounted for a small percentage of the overall group of sleep problems in this KAT6A population.…”

Underrecognized Sleep Disorders Across Rare Diseases: Real-world Insights From a Patient and Caregiver Summit

“…Among people with rare diseases, there is evidence that sleep disorders may be an underrecognized component of their disease burdens, particularly for neurological diseases (14). Studies suggest that while 25% of very young typical children have issues with sleep, that number increases to over 80% among children with neurodevelopmental disorders (15).…”