Sleep and intellectual disability …

Sleep Disorders

Updated 04.17.2024
Released 06.06.1994
Expires For CME 04.17.2027

Sleep and intellectual disability

Authors: Katelyn Bricker MD MS, Bradley V Vaughn MD

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Sleep and intellectual disability

In This Article

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Introduction

Overview

Individuals with intellectual disability, including children with neurodevelopmental disorders, are commonly affected by sleep disturbances. These sleep issues may manifest as typical sleep-related symptoms of insomnia or daytime sleepiness or as the appearance or exacerbation of disruptive daytime behaviors. The diagnosis and management of these sleep disorders, including sleep-disordered breathing, insomnia, hypersomnia, and circadian disorders, is part of the multidisciplinary approach to treatment. This article illustrates various sleep disorders associated with intellectual disability, including their etiology, diagnosis, and management.

Key points

	• Sleep issues are more common in patients with neurodevelopmental disorders than in the normal pediatric population.
	• Patients with intellectual disorders and sleep issues may present with common sleep-related symptoms, impaired learning, or the development or exacerbation of disruptive daytime behaviors.
	• Diagnosis of sleep issues requires careful history and judicious use of tools directed to identify the underlying sleep disorder.
	• Some sleep disorders may be a direct result of the underlying neurologic process.
	• Strategies for the management of sleep disorders in various syndromes associated with intellectual impairment vary depending on the etiology and manifestations.
	• Hypnotics and sedating medications have little use in the treatment of sleep disorders in the intellectually impaired. However, melatonin is advantageous when there are disturbances of the sleep-wake cycle.
	• Behavioral techniques for insomnia should be applied before medication in those with intellectual impairment.
	• Obstructive sleep apnea may improve with continuous positive airway pressure. However, procedures such as adenotonsillectomy are commonly indicated in children with intellectual impairment.

Historical note and terminology

Individuals with intellectual impairment have long been known to have frequent sleep issues (132). Bartlett described frequent sleep issues in a cohort of children with neurodevelopmental issues (14). These individuals commonly have sleep disturbances, including insomnia, hypersomnia, parasomnia, and sleep-disordered breathing (11). Intellectual disability was previously referred to as mental retardation and defined as “a disability characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and practical adaptive skills. This disability originates before age 18.” Criteria for the diagnosis of intellectual disability are described in The Diagnostic and Statistical Manual of Mental Disorders, TR, fifth edition (07).

Although sleep problems are recognized in children with intellectual disabilities, newer discoveries of sleep issues have uncovered more specific issues in each disorder. Various sleep disturbances are reported in disorders associated with intellectual disability and will be briefly described in the following conditions:

	• Angelman syndrome
	• Attention deficit and hyperactivity disorder
	• Autism spectrum disorders
	• Cerebral palsy
	• Down syndrome
	• Kleefstra syndrome
	• MBD5 haploinsufficiency syndrome
	• Mowat-Wilson syndrome
	• Prader-Willi syndrome
	• Rett syndrome
	• Smith-Magenis syndrome

A study focusing on determinants of sleep problems in children with intellectual disability found that comorbidities, such as recurrent pain, frequent seizures, and prescription of sleep medications, rather than functional abilities, were associated with poorer sleep, raising the possible benefit of improving sleep as part of the management strategy (48). Epileptic encephalopathies, which include epilepsy with continuous spike-wave during slow sleep, eg, Landau-Kleffner syndrome, are beyond the scope of this article, but are described elsewhere in MedLink Neurology.

Clinical manifestations

Presentation and course

	• Sleep disorders are commonly seen in monogenetic and polygenetic neurodevelopmental disorders.
	• Sleep disorders manifest in a spectrum of daytime and nighttime symptoms in individuals with intellectual disability.
	• The appearance or exacerbation of daytime and nighttime behavioral issues may hallmark the presence of underlying sleep disturbances.

Patients with intellectual ability commonly exhibit sleep disturbances, such as sleep disruption, hypersomnia, sleep-related breathing impairment, excessive nocturnal movement, parasomnias, circadian rhythm disorders, and irregular sleep-wake patterns. In addition to the traditional sleep-related symptoms, children, especially those with intellectual challenges, may manifest their sleep issues with changes in behavior. Typically, these include features of defiance or aggression, but they may also be more subtle, such as withdrawal or a decrease in new learning. For these patients, exacerbation of underlying dysfunctional behaviors may also be a clue to underlying sleep disruption. Although the direct impact of sleep disorders on neurodevelopmental issues is not well understood, untreated sleep disorders can worsen underlying neurologic problems. In a review, Barone and colleagues point out that sleep influences neuronal and synaptic regulation and, thus, sleep issues impact the brain in different ways across a child’s development (15). This may also account for more subtle influences of sleep on children (66).

Sleep disorders are included in the diagnostic criteria for many neurodevelopmental disorders (110). Studies have shown that up to 86% of patients who have neurodevelopmental disorders will experience sleep dysfunction (35). Challenges with sleep in this population include, but are not limited to, difficulty with sleep onset, nocturnal awakenings, and sleep fragmentation. Sleep disorders in children with neurodevelopmental dysfunction commonly last into adolescence and adulthood, unlike typically developing individuals (09). Several neurodevelopmental disorders have prominent concomitant sleep disturbances (110). Commonly seen across these disorders are greater restlessness in sleep, difficulty initiating or maintaining sleep, bedtime resistance, daytime sleepiness, difficulty awakening in the morning, or the emergence of sleep-related events, such as sleepwalking or sleep terrors. Some of these sleep issues may be associated with specific behavioral characteristics. These behavioral issues may be subtle, as the child becomes withdrawn or decreases in learning new tasks, or they may be more obvious symptoms, such as aggressive or defiant behaviors. Underlying behavioral issues can be more challenging in children with sleep problems and less responsive to standard interventions (125). Children may also show other physical changes, such as weight change, development of elevated blood pressure, decreased growth, or exacerbation of underlying epilepsy. As a result of the sleep disturbances, both children and their families suffer severe adverse effects on quality of life (19). Following is a more specific description of the sleep issues in each disorder.

Angelman syndrome. Angelman syndrome is characterized by intellectual disability, psychomotor delay, epilepsy, ataxia, speech impairment, and behavioral disturbance. Sleep dysfunction is common in Angelman syndrome, with sleep alterations being part of the diagnostic criteria for the disorder. Angelman syndrome is caused by a pathologic deletion of the UBE3A sleep-regulation gene on maternal chromosome 15 (77), which is thought to be involved in regulating sleep by regulating the accumulation of sleep-inducing chemicals during wakefulness (38). Sleep difficulties in this disorder manifest as arousals and awakenings during sleep, daytime somnolence, bruxism, hyperkinesia, enuresis, sleep terrors, snoring, and sleepwalking (113). An increased power in the delta frequencies on EEG during periods of wakefulness and overnight NREM sleep is nearly universally seen throughout the early development of these children (75). Polysomnography demonstrates 2 to 3 Hz poorly defined spike-wave complexes (85), reduced sleep efficiency, increased time in N3 sleep, reduced REM sleep, and decreased overall total sleep time as well as time spent in stage N2 sleep (75).

Attention deficit and hyperactivity disorder (ADHD). ADHD is diagnosed in approximately 5% of children (93). Sleep issues are frequently noted in over half of the individuals. Children and adolescents with ADHD tend to have sleep problems that may exacerbate or be the source of the ADHD symptoms and can affect quality of life for both the children and families (12). In previous diagnostic criteria (DSM-III-R), sleep issues were part of the diagnosis (06). For these patients, the severity of daytime issues appears to correlate with the severity of the sleep problems. This relationship has been the basis of several hypotheses involving a reciprocal relationship between ADHD and sleep. Patients with ADHD tend to have prolonged sleep latency, lower sleep efficiency, more nighttime awakenings, nighttime movement, and daytime sleepiness (99). The prolonged sleep latency and frequent awakenings may be related to underlying sleep issues. Delayed sleep phase syndrome is noted in some children with ADHD. Nighttime movement appears as periodic limb movement and as nonperiodic movement. The increase in movement may have several different explanations. Restless legs syndrome is also more frequently noted in children who carry the diagnosis of ADHD and is associated with periodic limb movements in sleep (34). Insomnia is a common finding in children with ADHD (135). The insomnia may be more frequent with a variety of issues, spanning from more stimulating sleep environments, associated psychiatric issues, and medication effect. Children have more disturbances in sleep with stimulant use. Insomnia is frequently noted when the patient is taking doses late in the day. This is supported by the notation that randomized controlled trials for stimulant medication in ADHD have higher rates of insomnia in the treatment arm than in placebo arms. Obstructive sleep apnea appears to have a bidirectional relationship with ADHD and is possibly present in over half of pediatric cases of ADHD (121). Although tonsillectomy has been shown to result in short-term improvement in patients with obstructive sleep apnea and ADHD, the longer-term lack of success suggests that the relationship goes beyond simple structural issues of the airway (121). ADHD symptoms have a direct correlation with sleep disorders, negatively affecting qualify of life, functionality, cognitive components, and behavior (86). Sleep disorders also appear to increase with ADHD combined with autism spectrum features (99).

Autism spectrum disorders. This lifelong neurodevelopmental disorder is characterized by persistent deficits in social communication, restricted interests, and repetitive patterns of behavior with abnormal sensory responses (07). Children and adolescents with autism spectrum disorder present with higher rates of sleep disturbances than the general population (64). Autism spectrum manifests as a variety of symptoms leading to multiple possible clinical presentations. The prevalence of sleep disorders in autism spectrum disorder ranges from 2% to 72%, and sleep disorders are observed more frequently in children than in adolescents (21). Problems with sleep include resisting bedtime, sleep initiation insomnia, nighttime and early morning awakenings, short sleep period, irregular sleep-wake pattern, poor sleep hygiene, bruxism, and restless sleep (133). Patients with autism spectrum disorder often have short sleep times, bedtime resistance, and reduced sleep pressure compared to those without autism spectrum disorder (33). The same study also highlighted a link between sleep difficulties and irritability, with deficits in social skills and behavioral problems.

A study by Favole and colleagues assessed the relationship between sleep disorders and emotional dysregulation in preschoolers affected by neurodevelopmental disorders, with and without autism spectrum disorder (42). Sleep disturbances are heavily associated with emotional dysregulation in children with neurodevelopmental disorders with or without autism spectrum disorder, both cross-sectionally and prospectively over time. The importance of sleep on emotional stability, the severity of sleep disturbance, and autism symptoms predicted the severity of emotional dysregulation over time.

Developmental delay and emotional/behavioral difficulties have been associated with insomnia (44). Tesfaye hypothesized that sleep is essential for the optimization of cognitive development, memory, and learning (119). Children with insomnia are more likely to show internalizing (anxiety/depressed symptoms), externalizing (aggressive/social problems), and global behavioral difficulties compared to those without sleep deprivation (44). The predilection for aggression in autism spectrum disorder may be heightened by insomnia (44). Children with autism spectrum disorder and sleep deprivation were negatively impacted in regard to intellectual ability and verbal skills and displayed more deficits in skills needed to complete typical daily living tasks, socialization skills, and motor development (118). These children also experienced more nighttime awakenings and sensitivity to sleep environment disturbances, such as noise (118). Individuals with autism tend to have longer sleep-onset latency, lower sleep efficiency, and decreased total sleep time as well as more sedentary lifestyle and lower daytime exposure to light (83). This same pattern was found in adults with autism spectrum disorder and associated with sedentary daily behavior and increased nocturnal activity (13).

Both symptoms of autism spectrum disorder and ADHD are associated with poor family function, increased parental stress, and poor mental health. The effects of parental stress may have bidirectional effects on sleep problems in children and negatively affect development (82). Petti and colleagues suggest that assessment of autism spectrum disorder symptomatology in youth with ADHD (and vice versa) in cases with sleep disruption is important because a high prevalence of ADHD is seen in patients with autism spectrum disorder and sleep disruption, and autism spectrum disorder symptoms are prevalent in patients presenting with ADHD (92).

Unfortunately, sleep problems in autism spectrum disorder tend to be associated with the severity of autism spectrum disorder symptoms. Therefore, the severity of autism spectrum disorder symptoms increases as sleep disturbances increase (106).

Cerebral palsy. This diagnosis is a collection of genetic and acquired childhood disorders that affects motor function, tone, and posture as a result of injury to the developing brain (130). Children with cerebral palsy, especially those who are nonambulatory, are more likely to have sleep problems than their typically developing peers (61). Cerebral palsy has also been associated with epilepsy, intellectual disability, communication issues, and sensory disturbances (91). Children with cerebral palsy may have risk factors (brain injury, physical disabilities) that make them more likely to have sleep problems when compared to typically developing children (58). The prevalence of sleep problems in children with cerebral palsy is high and has been reported in more than 40% of children with this disorder (76). A population-based study found the most common sleep issues to be difficulty initiating and maintaining sleep, reduced total sleep duration, daytime sleepiness, behavioral issues, nocturnal seizures, and pain. Pain is reported in this patient population, particularly in the most severely affected children, and may be a strong predictor for issues with initiation and maintenance of sleep.

Down syndrome. Also known as trisomy 21, Down syndrome is the most frequent genetic disorder and is associated with cognitive and physical impairments, including sleep disorders, obesity, hypotonia, and motor and neurologic developmental delays (69). Individuals across all ages with Down syndrome experience sleep problems. Sleep issues in Down syndrome can lead to significant behavioral and cognitive morbidities in this population (107). Sleep-disordered breathing is frequent in patients with Down syndrome, with a prevalence ranging from 60% to 95% (107). Children with Down syndrome have anatomical narrowing of the upper airway at different levels and are more prone to airway collapse leading to obstructive sleep apnea (81). They also have relative macroglossia due to small oral cavity, obesity, hypotonia of the pharyngeal muscles, and enlarged tonsils or adenoids. Compared with controls, children with Down syndrome evaluated by sleep nasopharyngoscopy have more pharyngeal and lingual collapse but less adenoidal hypertrophy (43). Respiratory instability appears early in life. These patients also have high prevalence for central apnea early in life and hypoventilation at various stages of development (41). More commonly seen in childhood and adolescents, obstructive apnea is a common feature. In one retrospective review, up to 82% of young adults with Down syndrome who underwent polysomnography were found to have obstructive sleep apnea, and one third were severe (29). In addition to sleep-related breathing issues, this population suffers from restless sleep, snoring, bruxism, frequent night awakenings, nocturnal enuresis, and daytime behavioral problems (hyperactivity) more than daytime sleepiness (81).

Kleefstra syndrome. Kleefstra syndrome is characterized by intellectual disability, childhood hypotonia, autistic-like features, and distinctive facial features (70). It is a rare genetic disorder caused by the loss of the EHMT1 gene or by mutations that disable this gene’s function. Sleep disturbance is described as frequent nocturnal and early morning awakenings and excessive daytime wakefulness. In adolescents and young adults, sleep disturbance may be a precursor for severe regression and possibly even the development of psychoses.

MBD5 haploinsufficiency syndrome. Characteristics of this neurodevelopmental disorder include developmental delay, intellectual disability, seizures, severe speech impairment, sleep disturbances, and abnormal behaviors (87). Sleep disturbances affect about 90% of children, consisting of frequent nighttime waking, short sleep duration, night terrors, and early morning awakenings.

Mowat-Wilson syndrome. Children with Mowat-Wilson syndrome, a genetic syndrome, are recognized by their square-shaped face, widely spaced deep-set eyes, a prominent pointed chin, and a broad nasal bridge with a rounded tip of the nose. In addition to the distinctive facial features, affected patients may have congenital heart defects, Hirschsprung disease, agenesis of the corpus callosum, limited or absent speech, microcephaly, seizures, and moderate to severe intellectual disability (04). This genetic disorder is caused by a heterozygous mutation or deletion of the ZEB2 gene (04). Sleep disturbances are common in Mowat-Wilson syndrome. Using the Sleep Disturbance Scale for Children, Evans found approximately 44% scored in the clinical disorder range and over half scored in the borderline range for at least one subscale (40). Over 29% of this cohort noted frequent movement issues near sleep-wake transitions and parasomnias at sleep-wake transitions. Therefore, this study suggests this population should be screened for sleep disorders.

In a study utilizing video polysomnography to analyze sleep structure, children with Mowat-Wilson demonstrated a reduction of total sleep time, an increase in wake after sleep onset, and increased arousal index when compared to controls (36). These findings could all be signs of disturbed sleep. The same study also noted a significant increase in the percentage of stage N3 sleep in children with Mowat-Wilson syndrome older than 7 years old, which may be attributable to the slowing of EEG background activity typical of this syndrome.

Prader-Willi syndrome. This genetic syndrome is a result of the absence of expression of the paternally active genes on the long arm of chromosome 15. From infancy, this syndrome is characterized by hypotonia, feeding difficulties, hypogonadism, characteristic facial features, and small hands and feet (57). Children then go on to develop intellectual disability, global developmental delay, behavioral concerns, sleep disturbance, hyperphagia, and obesity. Sleep disorders commonly affect patients with Prader-Willi syndrome, especially central sleep apnea, obstructive sleep apnea, features of narcolepsy with or without cataplexy, insomnia, and restless sleep (37).

Patients may suffer from both central and obstructive sleep apnea, and the prevalence of each may change with age. Central apnea is more prevalent in infants with Prader-Willi syndrome compared to older children (27). Up to 43% of infants with Prader-Willi syndrome have central sleep apnea, compared to approximately 5% of kids between the ages of 2 and 18 years (27). Sleep-disordered breathing, including obstructive sleep apnea, is present in more than 80% of children with Prader-Willi syndrome (24). In a retrospective review of 20 patients with Prader-Willi syndrome who had overnight polysomnography, the median AHI was 8.55 events/hour (03). Unfortunately, untreated obstructive sleep apnea in Prader-Willi syndrome is associated with more severe delays in developmental milestones in adolescents and young adults (89), among other behavioral concerns. Increasing BMI has been associated with more severe hypoxemia during sleep and more sleep disruptions (37).

Approximately half of those with Prader-Willi syndrome have REM sleep disorders that are considered phenotypic variations of narcolepsy, including sleep-onset REM periods, frequent arousals during REM sleep, and a significant increase in total REM sleep (55). This can be confounded by a high prevalence of excessive daytime sleepiness. Approximately 67% of adults with Prader-Willi syndrome have excessive daytime sleepiness (47), which is demonstrated by decreased wakefulness combined with increased time in stage N3 sleep during the day and night (129). Additionally, the prevalence of insomnia in Prader-Willi syndrome is approximately 29% (05). To complicate this further, disrupted sleep and awakenings may contribute to nighttime foraging for food in this population as well as inappropriately amplify the circadian drive for food at night (37).

Rett syndrome. This is a severe X-linked dominant neurodevelopmental disorder that predominantly affects females (117). It is caused by a mutation in the methyl-CpG-binding protein 2 (MeCP2) gene (131) and is characterized by poor growth, feeding difficulties, hyperventilation and breath holding, seizures, scoliosis, and disrupted sleep (50). The prevalence of sleep problems in Rett syndrome is estimated to be more than 80% (139). Patients with Rett syndrome have a high percentage of slow-wave sleep (108). In a large sample study of 237 cases from the Australian Rett syndrome database, Young and colleagues investigated sleep characteristics and found that these patients experienced laughter during the night, daytime naps, night screaming, bruxism, seizures, obstructive sleep apnea, delayed sleep onset, and reduced sleep efficiency (139). Epilepsy has been reported in 50% to 80% of cases (49). Frequent seizures are associated with poor sleep and fragmented sleep architecture (20).

Smith-Magenis syndrome. This syndrome is characterized by distinctive facial features, developmental delay, cognitive impairment, behavioral abnormalities, sleep disturbance, and obesity (111). It is the result of haploinsufficiency of the RAI1 (retinoic acid induced) gene mapping to chromosome 17p11.2, which regulates transcription of the circadian locomotor output cycles kaput (CLOCK) gene, resulting in disrupted circadian rhythmicity (134). Patients with Smith-Magenis syndrome have altered circadian rhythms (114) with an inverted (diurnal) pattern of melatonin characterized by elevated daytime and low nighttime melatonin levels (112). This results in less total night sleep, lower sleep efficiency, earlier sleep onset, earlier final wake times, increased waking after sleep onset, and increased daytime naps. Growth hormone deficiency has been implicated in the sleep disturbance in Smith-Magenis (62). Individuals with Smith-Magenis syndrome also have more sleep-disordered breathing than typically developing children, which may be attributable to their facial anatomy or to obesity-related ventilatory problems (28).

Prognosis and complications

A meta-analysis has shown that people with intellectual disabilities experience poorer quality and shorter sleep duration than their typically developing peers (116). Sleep problems tend to be chronic and can cause cognitive and behavioral difficulties that affect the entire family’s well-being (16). As the patient ages, the sleep issues may change and, thus, adjustment to these changes is necessary in hopes of improving sleep. Certain sleep behaviors are related to important developmental skills, including attention and listening (16). Poor sleep may lead to impairment of these skills, caregiver exhaustion, and increased likelihood of institutionalization.

Clinical vignette

A 6-year-old male with trisomy 21 presented with disruptive daytime behavior at school, more irritability at home, and snoring. The child also reverted to taking an afternoon nap. The pediatrician evaluated the child and noted tonsillar hypertrophy and a crowded oropharynx. The child also had a history of tonsillitis. The child was referred to the sleep clinic and was sent for overnight polysomnogram. Polysomnogram revealed an AHI of 9 (moderate obstructive sleep apnea) and multiple apnea-related arousals. The child was referred to ENT for adenotonsillectomy.

At 6 months following adenotonsillectomy, the child had a repeat polysomnogram showing an AHI of 2.1 and improvement of snoring. Daytime behavior improved, and the child stopped taking an afternoon nap. Due to the residual apnea and snoring, the child was placed on a nasal decongestant, which resolved the snoring.

Biological basis

Etiology and pathogenesis

	• Sleep disorder etiologies are multifactorial and often vary from one disorder to another.
	• Electrophysiological disturbances, irregularities of sleep-wake cycle, genetic variations, and comorbid medical conditions are frequent findings.

The etiology of sleep disturbances varies, and more than a single factor typically plays a role. However, some general statements can be made. Various factors that may contribute to sleep dysfunction in neurodevelopmental disorders include developmental delay, learning disabilities, psychiatric disturbances, seizure disorders, upper airway obstruction, gastroesophageal reflux, sensory issues, and physical deformities (18).

Sleep apnea. In Prader Willi syndrome, hypothalamic dysfunction, developmental brain abnormalities, craniofacial dysmorphia, hypotonia, obesity, and chest wall deformities can all contribute to the presence and severity of sleep-disordered breathing (10). In Down syndrome, factors that specifically contribute to obstructive sleep apnea include craniofacial abnormalities, such as midfacial and mandibular hypoplasia, narrow nasopharynx, and relative macroglossia, in addition to adenotonsillar hypertrophy, alteration in upper airway muscle tone, and obesity (81). Very young patients with Down syndrome tend to have an increased propensity for central apnea, which may be resultant of hypotonia and immature respiratory control (41). Other central nervous system factors may also influence the control of the upper and lower respiratory muscles in sleep, thus, increasing the likelihood of sleep apnea.

Hypercapnia. Adults with Prader-Willi syndrome often have abnormal hypercapnic ventilatory response (11), and children with the disorder have also been found to be hypercapnic (02). The severity of this hypoxic ventilatory response appears to be independent of the degree of obesity (137). These individuals tend to have lower nocturnal basal blood oxygen saturation levels (SpO2), with clusters of desaturations, compared to controls (65). Increased nocturnal hypoventilation may be a result of this poor ventilatory control as well as a loss of functional reserve capacity (02). Children have disproportionately longer periods of hypoventilation in comparison to typically developing children with the same AHI (02).

Sleep features and sleep state maintenance issues. Children with neurodevelopmental disorders and intellectual impairment may have select electrophysiological features of sleep—specifically, a vulnerability to abnormal spindle generation (52). Sleep spindles are generated from the thalamus and require specific neuronal relay to the cortex to function. Similarly, slow-wave generation is typically thought to involve cortical to cortical synchronization. Levin and colleagues found that low-frequency (2 to 4 Hz) delta rhythms were increased in Angelman syndrome during wake and during all stages of NREM sleep in overnight EEGs (75). Lower sleep efficiency REM ratios have been characterized as neurophysiological effects of Down syndrome, autism, and Angelman syndrome (39).

Although the mechanisms for the control of REM sleep are not completely understood, a relationship between the control of REM sleep and wake is thought to involve the neurotransmitter, hypocretin, also known as orexin. This neurotransmitter is primarily in the hypothalamus and appears to play a role in the maintenance of wakefulness and eating behavior. In Prader-Willi syndrome, some children are noted to have narcolepsy-like features and eating control issues. Failure to develop the hypocretin system has been hypothesized as a potential etiology for these patients (88).

Disturbances of the sleep-wake cycle. This topic is discussed in more detail in the MedLink article Irregular sleep-wake rhythm disorder. Irregular sleep-wake schedules often seen in children with severe intellectual impairment might be linked to the specific syndrome genotype or phenotype, an endogenous endocrine dysfunction or neurotransmitter release, or to an altered perception of environmental time cues (also known as zeitgebers) (09). These cues include the light-dark cycle, food schedule, maternal inputs, etc. Those with severe intellectual impairment often have underlying central nervous system pathology. This may result in difficulty perceiving time cues to entrain a sleep-wake cycle to a 24-hour day, such as regular mealtimes, activity, and social interactions.

Several hypotheses exist as to the underlying mechanism of sleep issues in autism spectrum disorders. Some researchers suggest that the melatonin pathway is impaired, causing insomnia in autism spectrum disorder. Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in autism spectrum disorders (126). Genes involved in melatonin and receptor function, lower melatonin concentrations, and altered melatonin circadian rhythm have all been assessed as contributing to autism spectrum disorder in a systematic review (105). Therefore, melatonin therapy has been a basis of treatment, with some success.

The overall sleep quality in intellectual disability is poor. A meta-analysis of sleep time revealed that people with intellectual disability slept for an average of 18 minutes less than people without (116).

Genetic variants. The TCF20 (transcription factor 20) gene encodes a transcriptional co-regulator structurally similar to RAI1, the gene responsible for Smith-Magenis syndrome. Pathogenic variants are associated with a novel syndrome with clinical characteristics similar to those in Smith-Magenis syndrome. Two pathogenic loss-of-function variants were recurrent in unrelated families, and patients presented with phenotypes illustrated as intellectual disability, hypotonia, dysmorphic features, and sleep disturbance (128).

The SNORD116 gene has been implicated in Prader-Willi syndrome (17). The gene is also implicated in sleep, as two individuals with small deletions in this gene exhibited increased REM/non-REM ratios, increased REM fragmentation, and increased amplitude of theta waves during REM sleep (74). Mice lacking the SNORD116 gene were found to have reduced gray matter volume in the ventral hippocampal areas and septum regions important for maintaining theta rhythms in the brain (74).

A study notes alterations in genes related to circadian rhythms, such as CLOCK genes, and melatonin levels (33). These patients also showed altered hypothalamic pituitary adrenal axis and autonomic functions, which may result in a propensity towards hyperarousal and hypersympathetic state.

Somatic abnormalities and comorbid conditions. Some of the disorders of intellectual impairment are associated with congenital malformations, such as craniofacial abnormalities. Predisposing factors to obstructive sleep apnea in Down syndrome include mandibular or maxillary hypoplasia, airway abnormalities (narrow nasopharynx, laryngomalacia, tracheomalacia), small upper airway, hypotonia, relative macroglossia, and obesity (63). Sleep disturbance may also be a result of medical comorbidity. Children with intellectual impairment and medical conditions tend to have more sleep disturbance than those with intellectual impairment without medical comorbidity (46).

Table 1. Sleep Disorder Etiology by Disorder

Disorder	Cause	Symptoms	Prevalence of sleep disorders
Angelman syndrome	Deletion of the UBE3A gene on maternal chromosome 15	Arousals/awakenings during sleep, irregular sleep-wake cycles, daytime somnolence, bruxism, hyperkinesia, enuresis, sleep terrors, snoring, sleepwalking	72% (113)
Attention deficit hyperactivity disorder		Prolonged sleep latency, low sleep efficiency, increase in wake after sleep onset, frequent awakenings and arousals, increased nocturnal movements	> 50% (99)
Autism spectrum disorder		Insomnia, nighttime and early morning awakenings, short sleep period, irregular sleep-wake pattern, poor sleep hygiene, bruxism, and restless sleep	2% to 72% (21)
Cerebral palsy		Difficulty initiating and maintaining sleep, nightly seizures disrupting sleep, reduced total sleep duration, daytime sleepiness, pain	23% to 50% (76)
Down syndrome	Gain of one additional copy of chromosome 21	Obstructive sleep apnea, central sleep apnea, restless sleep, snoring, bruxism, frequent night wakings, nocturnal enuresis, daytime behavioral problems	Obstructive sleep apnea: 60% to 95% (107)
Kleefstra syndrome	Loss of the EHMT1 gene	Frequent nocturnal and early morning awakenings, excessive daytime wakefulness
MBD5 haploinsufficiency	Heterozygous deletion of 2q23.1 encompassing the MBD5 gene	Frequent nighttime waking, short sleep duration, night terrors, early morning awakenings	90% (87)
Mowat-Wilson syndrome	Mutation or deletion of the ZEB2 gene	Sleep-wake transition disorders, reduction of total sleep time, increase in wake after sleep onset, increased arousal index	44% to 53% (40)
Prader-Willi syndrome	Absence of expression of the paternally active genes on the long arm of chromosome 15	Ventilatory control during sleep, central sleep apnea, obstructive sleep apnea, features of narcolepsy with or without cataplexy, insomnia, restless sleep	Insomnia: 29% (37) Sleep-disordered breathing: > 80% (24)
Rett syndrome	Mutation in the MeCP2 gene	Laughter during the night, daytime naps, night screaming, bruxism, seizures, obstructive sleep apnea, delayed sleep onset, reduced sleep efficiency	> 80% (139)
Smith-Magenis syndrome	Haploinsufficiency of the RAI1 gene on chromosome 17p11.2	Altered circadian rhythms with an inverted (diurnal) pattern of melatonin characterized by elevated daytime and low nighttime melatonin levels, less total night sleep, lower sleep efficiency, earlier sleep onset, earlier final wake times, increased waking after sleep onset, increased daytime naps	95% (111)

Prevention

	• Good sleep hygiene and risk factor reduction may help prevent some sleep issues, but clinicians must maintain vigilance for possible underlying sleep disorders.
	• A regular sleep schedule that accentuates bedtime routines may help improve signaling of the approach of sleep time.
	• Establishment of daytime activity, timed sunlight exposure, and regular mealtimes may help with daytime alertness.
	• Screening for sleep-disordered breathing and sleep dysfunction may help identify the problem in the early stages and prevent poor outcomes.

Sleep education and the implementation of healthy sleep practices is always the first-line intervention for children with sleep problems (59). Good sleep hygiene and appropriate limit-setting may prevent or reduce the severity of sleep disruption in intellectually disabled children. Children benefit from consistent bedtimes and wake times, even on weekends. If age appropriate, naps should be at a consistent time each day. Electronic devices, such as tablets, television, computer, or video games, should be avoided before bed and kept outside of the bedroom. Attention should be given to the sleep environment such that the bedroom is conducive for sleep. This environment should be dark, cool, quiet, comfortable, and absent of any stimulating devices or objects. Exercise during the day can help sleep and is best done earlier in the day rather than in the evening. Exercise and stimulating activities in the evening can delay the sleep phase. Diet can also play an important role; consistent mealtimes, a healthy diet, and avoidance of high sugar–containing foods may help with sleep. Avoid consumption of caffeinated beverages and products (sodas, chocolate, tea, coffee). Additionally, the child should be placed in bed drowsy but awake so that the association of sleep is made with the bedroom.

Obesity prevention may reduce the severity of sleep-disordered breathing in the intellectually impaired. Anatomical (such as craniofacial) abnormalities of the upper airways predispose to obstructive sleep apnea. It may be helpful to correct anatomical abnormalities of the upper airways that predispose to obstructive sleep apnea. Negative outcomes may be avoided if this population is frequently screened for sleep disturbance.

Differential diagnosis

Confusing conditions

The differential diagnosis of sleep disturbance in the intellectually impaired includes brain and brainstem dysfunction involved in sleep-wake regulation, circadian rhythm disorder, central or obstructive sleep apnea, nocturnal seizures, poor sleep hygiene, psychosocial factors, and medications. Patients with severe intellectual disability are more likely to have brain dysfunction as the cause. Snoring, witnessed apneas, and craniofacial abnormalities tend to favor a diagnosis of obstructive sleep apnea. Patients with blindness are more likely to have circadian rhythm disorders. When patients have daytime behavioral problems or major life stressors, including social issues at home or with caregivers, psychosocial issues should be suspected as a culprit for sleep disturbance.

Associated or underlying disorders

Children with Down syndrome often have undiagnosed obstructive sleep apnea. The prevalence of obstructive sleep apnea in Down syndrome has been reported to be as high as 66% in a large cohort study (80; 41). Even in those without a history of snoring or witnessed apnea, the prevalence was 53.8%. The potential negative consequences of obstructive sleep apnea include failure to thrive, pulmonary hypertension, fragmented sleep, and poor daytime cognitive functioning. The American Academy of Pediatrics recommends a polysomnogram in all children with Down syndrome at the age of 4 years or earlier when there is a history for upper airway obstruction during sleep (23).

Patients with Prader Willi syndrome frequently have underlying sleep-related breathing disorders, such as obstructive and central apnea. Excessive daytime sleepiness and REM sleep disorders (sleep-onset REM, REM sleep in naps, many arousals during REM, and significant decrease in total REM sleep) can also occur in Prader-Willi syndrome, similar to patients with narcolepsy (55). However, symptoms of cataplexy and sleep paralysis are rarely seen in these patients (37).

Diagnostic workup

	• Thorough sleep history, including the daytime and nighttime activities
	• Sleep-wake log
	• Actigraphy
	• Polysomnography
	• Thyroid function

The cornerstone of delineating any sleep issue is a thorough history and physical exam. The history should review the symptoms, time course, things that aggravate and relieve the symptoms, medications and supplements, features of the sleep, sleep environment and sleep routine, and daily habits. Also, typical diagnostic workup for a patient with disrupted sleep includes a sleep-wake diary. Actigraphy is beneficial in measuring circadian rhythms and is applicable in adults with intellectual disability (53). A polysomnogram will aid in identifying physiological changes during sleep, but this will not measure total sleep as the sleep laboratory is not the home environment. These tests should be obtained when sleep-disordered breathing, movement issues, or other nighttime issues are suspected. Typically, these studies are technically challenging and, thus, should be performed in a laboratory with technologists and sleep physicians who are experienced in handling these patients. Due to the high likelihood of sleep-disordered breathing in this population, these studies should include measurement of carbon dioxide, and there should be a low threshold to perform these studies.

Hypothyroidism may be a contributor to obstructive sleep apnea, though the mechanisms are not completely clear (73). Because hypothyroidism is also prevalent in Down syndrome and other syndromes with intellectual impairment, thyroid function should be assessed in intellectually impaired children with sleep-disordered breathing (08).

Management

	• There are no specific guidelines for most sleep disorders with intellectual impairment.
	• Behavioral programs are typically first-line, followed by sleep medications if no correctible cause, such as obstructive sleep apnea, is identified.
	• Nutritional interventions may improve sleep in patients with intellectual impairment.
	• Melatonin by be useful in regulating the circadian rhythm. Hypnotics and benzodiazepines have minimal use.
	• Surgical options and device therapy may be beneficial for children with Down syndrome who have persistent obstructive sleep apnea after adenotonsillectomy and failed CPAP.

Behavioral techniques. The recognition and treatment of sleep disorders is crucial for the management of children with neurodevelopmental disorders and may have a positive impact on their daytime behavior (16). Behavioral approaches focusing on good sleep hygiene and regularly scheduled sleeping hours with minimization of daytime sleep are important in the treatment of insomnia. In situations in which an underlying sleep pathology is ruled out, initiation of behavioral therapy may be beneficial in the treatment of disturbed sleep and chronic insomnia (37). A meta-analysis found that behavioral interventions can be helpful to improving sleep problems in those with intellectual disability (95).

Research on children with ADHD and sleep issues shows beneficial effects from non-pharmacological behavioral interventions and sleep management programs, such as implementation of healthy sleep practices, graduated extinction, reinforcement, and faded bedtime (100; 109). Other research around ADHD indicates lifestyle factors, such as physical activity, could have an influence on sleep latency (time it takes to transition from wake to sleep). Regular physical activity may be a beneficial accompanying therapy (98).

No single intervention has been proven to be effective across all sleep problems in children with autism. Behavioral techniques, melatonin, and parent education/education program interventions were the most effective in treating autistic patients with multiple domains of sleep problems compared to other interventions. Some of these interventions included a combination of the following: extinction (standard and graduated), sleep hygiene, positive reinforcement, chronotherapy, sleep restriction, cueing, stimulus fading, scheduled awakening, and faded bedtime with response cost (30). Some alternative therapies included massage therapy and aromatherapy as well as iron supplementation (30). Children with autism also tend to prefer a weighted blanket but do not improve objective or subjective measures of insomnia (51).

Nutritional interventions. Harper and colleagues found that dietary patterns can be an important factor in improving the quantity and quality of sleep in the intellectually impaired (54). Individuals with intellectual disabilities are commonly lower in essential vitamins, minerals and whole grains, and fruits and vegetables. A healthy, balanced diet may help with sleep. As with the general population, a reduction in caffeine can help with sleep. However, there is not enough current evidence to recommend specific foods nor nutraceuticals to help with sleep in this population. In Prader-Willi syndrome, improving food security in the home may improve anxiety and sleep disruptions (37).

Pharmacotherapy. Sleep issues in those with intellectual impairment are typically chronic, rendering hypnotics and other sedating medications of limited use. Patients may develop tolerance to the sleep-inducing medications and suffer daytime sleepiness or increased cognitive impairment as a result. Discontinuation of these medications may result in rebound insomnia.

There are no FDA-approved therapeutic sleep aids to treat sleep disturbances in autism spectrum disorder. The neural mechanisms underlying sleep dysfunction in children with autism spectrum disorder are not fully understood; therefore, it is challenging to develop targeted therapeutics. Medications used in the treatment of sleep disorders and autism spectrum disorder include melatonin analogues, alpha-2 adrenergic agonists, antihistamines, antidepressants, and antipsychotics (84).

Kleefstra syndrome is an exception to the typical approach of starting treatment with behavioral interventions. In three case studies of Kleefstra syndrome, severe regression presented after sleep disturbances. Treatment with the usual behavioral programs and sleep medication resulted in intellectual deterioration. However, rapid treatment with high-dose antipsychotics restored sleep, prevented further regression, and improved functioning of daily life (127).

Melatonin is a key regulator of the circadian rhythm. Melatonin promotes sleep onset and the timing of other circadian functions, and it is involved in immune regulation (124), but it does not have a role in decreasing nighttime awakenings. Evidence suggests impaired regulation of melatonin production in children with autism spectrum disorder (71). In Smith-Magenis syndrome, melatonin production is shifted to the daytime hours. Melatonin replacement therapy has been an approach in disorders such as Smith-Magenis syndrome and autism (78). Melatonin has been shown to significantly decrease sleep latency, with little impact on duration of sleep or behavior (68). A combination of nocturnal melatonin and daytime administration of acebutolol, an adrenergic melatonin antagonist, may be beneficial in increasing nocturnal melatonin concentrations and improving nocturnal sleep (32). A randomized, double-blind, placebo-controlled study found that nightly prolonged-release melatonin at a dose of 2, 5, or 10 mg is safe and effective for long-term treatment in children and adolescents with autism and insomnia (78). No detrimental effects on growth or pubertal development were observed, and there were no withdrawal or safety issues on discontinuation of melatonin. A meta-analysis by Xiong and colleagues found that melatonin was effective in treating insomnia in children with autism spectrum disorder through shortening of sleep onset latency, reduced frequency of night awakenings, and prolonged total sleep time (136). In a double-blind, placebo-controlled crossover study, patients treated with tasimelteon for 4 weeks demonstrated a significant improvement in sleep (94). In a randomized, placebo-controlled study of eight children with Angelman syndrome and idiopathic chronic insomnia, melatonin advanced sleep onset by 28 minutes, decreased sleep latency by 32 minutes, increased total sleep time by 56 minutes, and reduced the number of nights with wakes from 3.1 to 1.6 nights per week (22). Notably, melatonin may have a protective role in neurodevelopmental disorders due to hypnotic, anti-inflammatory, chronobiotic, and antioxidant effects. It may affect neurodevelopment given its effects on early synaptic plasticity and neurotransmitter levels (138).

Melatonin has been found to advance circadian rhythms in patients with ADHD, and endogenous melatonin can enhance total sleep time in these children; however, it does not affect the problem behavior, cognitive performance, or quality of life (123). Overall, ADHD medications trend toward worsening sleep. A 2023 systematic review suggested that drugs used for the treatment of ADHD often have negative consequences on sleep quality in this group; however, atomoxetine may have lesser effects on sleep compared to other medications (102).

In a case series of three children with Prader-Willi syndrome, excessive daytime sleepiness was treated with the histamine 3 receptor agonist pitolisant. The study observed that pitolisant decreased daytime sleepiness and improved cognition as shown by increased processing speed and improved mental clarity (97). It has been suggested that pitolisant may relieve some of the cognitive disability, excessive daytime sleepiness, and poor-quality nighttime sleep associated with Prader-Willi syndrome (97). Modafinil has also been effective in treating excessive daytime sleepiness in some children with Prader-Willi syndrome (31).

Trofinetide is the first U.S. FDA-approved medication for the treatment of Rett syndrome. Though not well established, its mechanism is thought to improve synaptic functioning and neuronal morphology (60). Trofinetide is a novel synthetic analog of glycine-proline-glutamate (GPE), a naturally occurring protein in the brain that partially reverses the primary symptoms in MECP2-deficient mice. GPE has also been found to improve motor function, respiratory function, and heart rate as well as increase brain weight and extend life span in mice (120).

Surgical therapy. CPAP can be efficacious in the treatment of obstructive sleep apnea for some children, though it has a relatively low patient adherence rate, limiting its overall usefulness (79). Hypoglossal nerve stimulation is a surgical treatment option that has been FDA approved for use in children with Down syndrome and persistent obstructive sleep apnea after adenotonsillectomy. A retrospective study of 53 patients with Down syndrome and persistent obstructive sleep apnea who underwent hypoglossal nerve stimulation found a total of 17 nonserious and 13 serious adverse events (25). Serious adverse events included readmission (for pain, cellulitis, and device extrusion), reoperation (for battery depletion), and pressure ulcer formation. Hypoglossal nerve stimulation may be a much needed therapy for children with Down syndrome and persistent obstructive sleep apnea after adenotonsillectomy. A systematic review of hypoglossal nerve stimulator in adolescents with Down syndrome and persistent obstructive sleep apnea showed promising findings (103). Hypoglossal nerve stimulator significantly improved sleep-disordered breathing, qualify of life, and neurocognitive measures in these children.

Sleep-related breathing disorders

Adenotonsillectomy for obstructive sleep apnea. Adenotonsillectomy is the standard of treatment for obstructive sleep apnea in children without intellectual impairment and has a typical success rate of 71% to 87% (01). Children with Prader-Willi syndrome undergoing adenotonsillectomy for obstructive sleep apnea show improvements in polysomnography and quality of life. Despite improvements, these children tend to have a substantial risk of postoperative complications requiring additional interventions, especially velopharyngeal insufficiency, and many have residual obstructive sleep apnea (26). In Down syndrome, the success rate of adenotonsillectomy is poor, and persistent obstructive sleep apnea is observed in 30% to 50% of children (67). A prospective study found that drug-induced sleep endoscopy (DISE)-directed treatment may be a useful method for the detection and treatment of the cause of upper airway obstruction in children with Down syndrome after adenotonsillectomy (01). Lingual tonsillectomy is another surgical treatment option for patients with Down syndrome and persistent airway obstruction following adenotonsillectomy (96).

Sleep apnea and hypoventilation

Continuous positive airway pressure (CPAP). Given the high rate of residual obstructive sleep apnea following adenotonsillectomy in children with disorders such as Prader-Willi and Down syndrome, CPAP is often the next step. CPAP is also a primary therapy for obesity-related hypoventilation. Although consistent CPAP usage has been found to reduce the severity of obstructive sleep apnea, compliance to treatment is an issue (72). Children with Down syndrome may be good candidates for bilevel positive airway pressure (BIPAP) when CPAP is not adequate as they tend to have hypoventilation that is out of proportion to the severity of their obstructive sleep apnea (45). Autism spectrum disorder is a common comorbidity in children with Down syndrome, and sensory issues may require mask desensitization and acclimation of the mask before adherence is possible (90). Even adults with Down syndrome struggle with adherence to CPAP therapy. A prospective trial of CPAP in community-dwelling adults with Down syndrome and obstructive sleep apnea showed that CPAP use led to improvements in subjective sleepiness, behavioral and emotional outcomes, and cognitive function in those with moderate to severe intellectual disability (56). Partial neural recovery can occur during short periods of treatment with CPAP. Adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness and improved verbal episodic memory in patients with obstructive sleep apnea can occur with 1 month of CPAP treatment (104). Similarly, noninvasive ventilation appears to be beneficial in treating obesity hypoventilation and obstructive sleep apnea in Smith-Magenis syndrome (28).

When a patient with intellectual disability develops obstructive sleep apnea, the need for CPAP management, or difficulty with sleep that is outside of the scope of the primary care physician, consider referral to a sleep center.

In some patients, central apneas are not responsive to PAP therapy. A retrospective cohort study found that oxygen therapy improved central sleep-disordered breathing and oxygenation in infants with Prader-Willi syndrome and central sleep apnea (122).

A multidisciplinary approach, including a sleep specialist, can be helpful in the management of many of these complex patients.

References

01: Abdel-Aziz M, Abdel-Naseer U, Elshahawy E, Elsherbeeny M, Nassar A. Persistent obstructive sleep apnea in children with Down syndrome after adenotonsillectomy: drug induced sleep endoscopy-directed treatment. J Craniofac Surg 2022;33:e185-7. PMID 35385239
02: Abel F, Tan HL, Negro V, et al. Hypoventilation disproportionate to OSAS severity in children with Prader-Willi syndrome. Arch Dis Child 2019;104(2):166-71. PMID 30007944
03: Abushahin A, Al-Naimi A, Abu-Hasan M, et al. Prevalence of sleep-disordered breathing in Prader-Willi syndrome. Can Respir J 2023;2023:9992668. PMID 37927914
04: Adam MP, Conta J, Bean LJH. Mowat-Wilson syndrome. In: GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle, 2019. PMID 20301585
05: Agar G, Brown C, Sutherland D, Coulborn S, Oliver C, Richards C. Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile. Mol Autism 2021;12(1):18. PMID 33632309
06: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd edition revised. Washington, DC: American Psychiatric Association, 1987.
07: American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM−5-TR). Washington, DC: American Psychiatric Association, 2022.
08: Amr NH. Thyroid disorders in subjects with Down syndrome: an update. Acta Biomed 2018;89(1):132-9. PMID 29633736
09: Angriman M, Caravale B, Novelli L, Ferri R, Bruni O. Sleep in children with neurodevelopmental disabilities. Neuropediatrics 2015;46(3):199-210. PMID 25918987
10: Angulo MA, Butler MG, Cataletto ME. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Invest 2015;38(12):1249-63. PMID 26062517
11: Arens R, Gozal D, Omlin KJ, et al. Hypoxic and hypercapnic ventilatory responses in Prader-Willi syndrome. J Appl Physiol (1985) 1994;77(5):2224-30. PMID 7868438
12: Arias-Mera C, Paillama-Raimán D, Lucero-González N, Leiva-Bianchi M, Avello-Sáez D. Relation between sleep disorders and attention deficit disorder with hyperactivity in children and adolescents: a systematic review. Res Dev Disabil 2023;137:104500. PMID 37075589
13: Ballester P, Martínez MJ, Javaloyes A, et al. Sleep problems in adults with autism spectrum disorder and intellectual disability. Autism Res 2019;12(1):66-79. PMID 30273974
14: Bartlett LB, Rooney V, Spedding S. Nocturnal difficulties in a population of mentally handicapped children. Br J Ment Subnormality 1985;31:54-9.
15: Barone I, Hawks-Mayer H, Lipton JO. Mechanisms of sleep and circadian ontogeny through the lens of neurodevelopmental disorders. Neurobiol Learn Mem 2019;160:160-72. PMID 30668981
16: Belli A, Breda M, Di Maggio C, Esposito D, Marcucci L, Bruni O. Children with neurodevelopmental disorders: how do they sleep? Curr Opin Psychiatry 2022;35(5):345-51. PMID 35165244
17: Bieth E, Eddiry S, Gaston V, et al. Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi syndrome. Eur J Hum Genet 2015;23(2):252-5. PMID 24916642
18: Blackmer AB, Feinstein JA. Management of sleep disorders in children with neurodevelopmental disorders: a review. Pharmacotherapy 2016;36(1):84-98. PMID 26799351
19: Boban S, Leonard H, Wong K, Wilson A, Downs J. Sleep disturbances in Rett syndrome: impact and management including use of sleep hygiene practices. Am J Med Genet A 2018;176(7):1569-77. PMID 29704311
20: Boban S, Wong K, Epstein A, et al. Determinants of sleep disturbances in Rett syndrome: novel findings in relation to genotype. Am J Med Genet A 2016;170(9):2292-300. PMID 27255190
21: Bougeard C, Picarel-Blanchot F, Schmid R, Campbell R, Buitelaar J. Prevalence of autism spectrum disorder and co-morbidities in children and adolescents: a systematic literature review. Front Psychiatry 2021;12:744709. PMID 34777048
22: Braam W, Didden R, Smits MG, Curfs LMG. Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial. J Child Neurol 2008;23(6):649-54. PMID 18539989
23: Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics 2011;128(2):393-406. PMID 21788214
24: Canora A, Franzese A, Mozzillo E, Fattorusso V, Bocchino M, Sanduzzi A. Severe obstructive sleep disorders in Prader-Willi syndrome patients in southern Italy. Eur J Pediatr 2018;177(9):1367-70. PMID 29318372
25: Chieffe D, Liu RH, Hartnick C. Challenges and adverse events in pediatric hypoglossal nerve stimulation. Int J Pediatr Otorhinolaryngol 2024;176:111831. PMID 38113620
26: Clements AC, Dai X, Walsh JM, et al. Outcomes of adenotonsillectomy for obstructive sleep apnea in Prader-Willi syndrome: systematic review and meta-analysis. Laryngoscope 2021;131(4):898-906. PMID 33026674
27: Cohen M, Hamilton J, Narang I. Clinically important age-related differences in sleep related disordered breathing in infants and children with Prader-Willi Syndrome. PLoS One 2014;9(6):e101012. PMID 24979549
28: Connor V, Zhao S, Angus R. Non-invasive ventilation for sleep-disordered breathing in Smith-Magenis syndrome. BMJ Case Rep 2016;2016:bcr2016215621. PMID 27495174
29: Cornacchia M, Sethness J, Alapat P, Lin YH, Peacock C. The prevalence of OSA among an adult population with Down syndrome referred to a medical clinic. Am J Intellect Dev Disabil 2019;124(1):4-10. PMID 30715921
30: Cuomo BM, Vaz S, Lee EAL, Thompson C, Rogerson JM, Falkmer T. Effectiveness of sleep-based interventions for children with autism spectrum disorder: a meta-synthesis. Pharmacotherapy 2017;37(5):555-78. PMID 28258648
31: De Cock VC, Diene G, Molinas C, et al. Efficacy of modafinil on excessive daytime sleepiness in Prader-Willi syndrome. Am J Med Genet A 2011;155A:1552-7. PMID 21671379
32: De Leersnyder H, Bresson JL, de Blois MC, et al. Beta 1-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith-Magenis syndrome. J Med Genet 2003;40(1):74-8. PMID 12525548
33: Dell'Osso L, Massoni L, Battaglini S, Cremone IM, Carmassi C, Carpita B. Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder. Ann Gen Psychiatry 2022;21(1):13. PMID 35534878
34: DelRosso LM, Picchietti DL, Spruyt K, et al. Restless sleep in children: a systematic review. Sleep Med Rev 2021;56:101406. PMID 33341437
35: Didden R, Sigafoos J. A review of the nature and treatment of sleep disorders in individuals with developmental disabilities. Res Dev Disabil 2001;22(4):255-72. PMID 11523951
36: Di Pisa V, Provini F, Ubertiello S, et al. Sleep in Mowat-Wilson syndrome: a clinical and video-polysomnographic study. Sleep Med 2019;61:44-51. PMID 31285160
37: Duis J, Pullen LC, Picone M, et al. Diagnosis and management of sleep disorders in Prader-Willi syndrome. J Clin Sleep Med 2022;18(6):1687-96. PMID 35172921
38: Ehlen JC, Jones KA, Pinckney L, et al. Maternal Ube3a loss disrupts sleep homeostasis but leaves circadian rhythmicity largely intact. J Neurosci 2015;35(40):13587-98. PMID 26446213
39: Esposito M, Carotenuto M. Intellectual disabilities and power spectra analysis during sleep: a new perspective on borderline intellectual functioning. J Intellect Disabil Res 2014;58(5):421-9. PMID 23517422
40: Evans E, Mowat D, Wilson M, Einfeld S. Sleep disturbance in Mowat-Wilson syndrome. Am J Med Genet A 2016;170(3):654-60. PMID 26686679
41: Fan Z, Ahn M, Roth HL, Li L, Vaughn BV. Sleep apnea and hypoventilation in patients with Down syndrome: analysis of 144 polysomnogram studies. Children (Basel) 2017;4(7):55. PMID 28665356
42: Favole I, Davico C, Marcotulli D, et al. Sleep disturbances and emotional dysregulation in young children with autism spectrum, intellectual disability, or global developmental delay. Sleep Med 2023;105:45-52. PMID 36963320
43: Fung E, Witmans M, Ghosh M, Cave D, El-Hakim H. Upper airway findings in children with Down syndrome on sleep nasopharyngoscopy: case-control study. J Otolaryngol Head Neck Surg 2012;41(2):138-44. PMID 22569015
44: Galli J, Loi E, Visconti LM, et al. Sleep disturbances in children affected by autism spectrum disorder. Front Psychiatry 2022;13:736696. PMID 35250655
45: Gastelum E, Cummins M, Singh A, Montoya M, Urbano GL, Tablizo MA. Treatment considerations for obstructive sleep apnea in pediatric Down syndrome. Children (Basel) 2021;8(11):1074. PMID 34828787
46: Ghanizadeh A, Faghih M. The impact of general medical condition on sleep in children with mental retardation. Sleep Breath 2011;15(1):57-62. PMID 19898883
47: Ghergan A, Coupaye M, Leu-Semenescu S, et al. Prevalence and phenotype of sleep disorders in 60 adults with Prader-Willi syndrome. Sleep 2017;40(12). PMID 29294134
48: Gilbertson M, Richardson C, Eastwood P, et al. Determinants of sleep problems in children with intellectual disability. J Sleep Res 2021;30(5):e13361. PMID 34032327
49: Glaze DG, Percy AK, Skinner S, et al. Epilepsy and the natural history of Rett syndrome. Neurology 2010;74(11):909-12. PMID 20231667
50: Gold WA, Krishnarajy R, Ellaway C, Christodoulou J. Rett syndrome: a genetic update and clinical review focusing on comorbidities. ACS Chem Neurosci 2018;9(2):167-76. PMID 29185709
51: Gringras P, Green D, Wright B, et al. Weighted blankets and sleep in autistic children--a randomized controlled trial. Pediatrics 2014;134(2):298-306. PMID 25022743
52: Gruber R, Wise MS. Sleep spindle characteristics in children with neurodevelopmental disorders and their relation to cognition. Neural Plast 2016;2016:4724792. PMID 27478646
53: Hare DJ, Jones S, Evershed K. Objective investigation of the sleep-wake cycle in adults with intellectual disabilities and autistic spectrum disorders. J Intellect Disabil Res 2006;50(Pt 10):701-10. PMID 16961699
54: Harper L, Ooms A, Wijne IT. The impact of nutrition on sleep in people with an intellectual disability: an integrative literature review. J Appl Res Intellect Disabil 2021;34(6):1393-407. PMID 34212459
55: Helbing-Zwanenburg B, Kamphuisen HA, Mourtazaev MS. The origin of excessive daytime sleepiness in the Prader-Willi syndrome. J Intellect Disabil Res 1993;37(Pt 6):533-41. PMID 8123999
56: Hill EA, Fairley DM, Williams LJ, Spanò G, Cooper SA, Riha RL. Prospective trial of CPAP in community-dwelling adults with Down syndrome and obstructive sleep apnea syndrome. Brain Sci 2020;10(11):844. PMID 33198148
57: Holm VA, Cassidy SB, Butler MG, et al. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 1993;91(2):398-402. PMID 8424017
58: Horwood L, Li P, Mok E, Shevell M, Constantin E. A systematic review and meta-analysis of the prevalence of sleep problems in children with cerebral palsy: how do children with cerebral palsy differ from each other and from typically developing children? Sleep Health 2019;5(6):555-71. PMID 31740377
59: Howlett M, Jemcov A, Adams A, et al. ABCs of SLEEPING tool: improving access to care for pediatric insomnia. Clin Pract Pediatr Psychol 2020;8:1-12.
60: Hudu SA, Elmigdadi F, Qtaitat AA, et al. Trofinetide for Rett syndrome: highlights on the development and related inventions of the first USFDA-approved treatment for rare pediatric unmet medical need. J Clin Med 2023;12:5114. PMID 37568516
61: Hulst RY, Gorter JW, Voorman JM, et al. Sleep problems in children with cerebral palsy and their parents. Dev Med Child Neurol 2021;63(11):1344-50. PMID 33990937
62: Itoh M, Hayashi M, Hasegawa T, Shimohira M, Kohyama J. Systemic growth hormone corrects sleep disturbance in Smith-Magenis syndrome. Brain Dev 2004;26(7):484-6. PMID 15351087
63: Jayaratne YSN, Elsharkawi I, Macklin EA, et al. The facial morphology in Down syndrome: a 3D comparison of patients with and without obstructive sleep apnea. Am J Med Genet A 2017;173(11):3013-21. PMID 28815893
64: Johnson KP, Zarrinnegar P. Autism spectrum disorder and sleep. Child Adolesc Psychiatr Clin N Am 2021;30(1):195-208. PMID 33223062
65: Kaditis AG, Polytarchou A, Moudaki A, Panaghiotopoulou-Gartagani P, Kanaka-Gantenbein C. Measures of nocturnal oxyhemoglobin desaturation in children with neuromuscular disease or Prader-Willi syndrome. Pediatr Pulmonol 2020;55(8):2089-96. PMID 32525614
66: Kamara D, Beauchaine TP. A review of sleep disturbances among infants and children with neurodevelopmental disorders. Rev J Autism Dev Disord 2020;7(3):278-94. PMID 33344102
67: Kanamori G, Witter M, Brown J, Williams-Smith L. Otolaryngologic manifestations of Down syndrome. Otolaryngol Clin North Am 2000;33(6):1285-92. PMID 11449787
68: Kaplan KA, Elsea SH, Potocki L. Management of sleep disturbances associated with Smith-Magenis syndrome. CNS Drugs 2020;34(7):723-30. PMID 32495322
69: Karmiloff-Smith A, Al-Janabi T, D'Souza H, et al. The importance of understanding individual differences in Down syndrome. F1000Res 2016;5:F1000. PMID 27019699
70: Kleefstra T, de Leeuw N. Kleefstra syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 2010. PMID 20945554
71: Kotagal S, Broomall E. Sleep in children with autism spectrum disorder. Pediatr Neurol 2012;47(4):242-51. PMID 22964437
72: Landete P, Soriano JB, Aldave B, et al. Obstructive sleep apnea in adults with Down syndrome. Am J Med Genet A 2020;182(12):2832-40. PMID 32909685
73: Lanfranco F. Sleep apnea syndrome and hypothyroidism. Endocrine 2013;44(3):551-2. PMID 24114404
74: Lassi G, Priano L, Maggi S, et al. Deletion of the Snord116/SNORD116 alters sleep in mice and patients with Prader-Willi syndrome. Sleep 2016;39(3):637-44. PMID 26446116
75: Levin Y, Hosamane NS, McNair TE, et al. Evaluation of electroencephalography biomarkers for Angelman syndrome during overnight sleep. Autism Res 2022;15(6):1031-42. PMID 35304979
76: Lowing K, Gyllensvärd M, Tedroff K. Exploring sleep problems in young children with cerebral palsy - a population-based study. Eur J Paediatr Neurol 2020;28:186-92. PMID 32669213
77: Madaan M, Mendez MD. Angelman syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022. PMID 32809705
78: Malow BA, Findling RL, Schroder CM, et al. Sleep, growth, and puberty after 2 years of prolonged-release melatonin in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 2021;60(2):252-61. PMID 31982581
79: Marcus CL, Rosen G, Ward SL, et al. Adherence to and effectiveness of positive airway pressure therapy in children with obstructive sleep apnea. Pediatrics 2006;117(3):e442-51. PMID 16510622
80: Maris M, Verhulst S, Wojciechowski M, Van de Heyning P, Boudewyns A. Prevalence of obstructive sleep apnea in children with Down syndrome. Sleep 2016a;39(3):699-704. PMID 26612391
81: Maris M, Verhulst S, Wojciechowski M, Van de Heyning P, Boudewyns A. Sleep problems and obstructive sleep apnea in children with down syndrome, an overview. Int J Pediatr Otorhinolaryngol 2016b;82:12-5. PMID 26857307
82: Martin CA, Papadopoulos N, Chellew T, Rinehart NJ, Sciberras E. Associations between parenting stress, parent mental health and child sleep problems for children with ADHD and ASD: systematic review. Res Dev Disabil 2019;93:103463. PMID 31446370
83: Martinez-Cayuelas E, Rodríguez-Morilla B, Soriano-Guillén L, Merino-Andreu M, Moreno-Vinués B, Gavela-Pérez T. Sleep problems and circadian functioning in children and adolescents with autism spectrum disorder. Pediatr Neurol 2022;126:57-64. PMID 34740134
84: Maurer JJ, Choi A, An I, Sathi N, Chung S. Sleep disturbances in autism spectrum disorder: animal models, neural mechanisms, and therapeutics. Neurobiol Sleep Circadian Rhythms 2023;14:100095. PMID 37188242
85: Miano S, Bruni O, Leuzzi V, Elia M, Verrillo E, Ferri R. Sleep polygraphy in Angelman syndrome. Clin Neurophysiol 2004;115(4):938-45. PMID 15003776
86: Moreau V, Rouleau N, Morin CM. Sleep of children with attention deficit hyperactivity disorder: actigraphic and parental reports. Behav Sleep Med 2014;12(1):69-83. PMID 23473239
87: Mullegama SV, Mendoza-Londono R, Elsea SH. MBD5 haploinsufficiency. In: Adam MP, Everman DB, Mirzaa GM, et al, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 2022. PMID 27786435
88: Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev 2005;9(4):269-310. PMID 16006155
89: O’Donoghue FJ, Camfferman D, Kennedy JD, et al. Sleep-disordered breathing in Prader-Willi syndrome and its association with neurobehavioral abnormalities. J Pediatr 2005;147(6):823-9. PMID 16356439
90: Oxelgren UW, Myrelid A, Annerén G, et al. Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study. Dev Med Child Neurol 2017;59(3):276-83. PMID 27503703
91: Paul S, Nahar A, Bhagawati M, Kunwar AJ. A review on recent advances of cerebral palsy. Oxid Med Cell Longev 2022;2622310. PMID 35941906
92: Petti T, Gupta M, Fradkin Y, Gupta N. Management of sleep disorders in autism spectrum disorder with co-occurring attention-deficit hyperactivity disorder: update for clinicians. BJPsych Open 2023;10(1):e11. PMID 38088185
93: Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol 2014;43(2):434-42. PMID 24464188
94: Polymeropoulos CM, Brooks J, Czeisler EL, et al. Tasimelteon safely and effectively improves sleep in Smith-Magenis syndrome: a double-blind randomized trial followed by an open-label extension. Genet Med 2021;23(12):2426-32. PMID 34316024
95: Priday LJ, Byrne C, Totsika V. Behavioural interventions for sleep problems in people with an intellectual disability: a systematic review and meta-analysis of single case and group studies. J Intellect Disabil Res 2017;61(1):1-15. PMID 26952339
96: Prosser JD, Sally RS, Oscar R, Simakajornboon N, Meinzen-Derr J, Ishman SL. Polysomnographic outcomes following lingual tonsillectomy for persistent obstructive sleep apnea in Down syndrome. Laryngoscope 2017;127(2):520-4. PMID 27515709
97: Pullen LC, Picone M, Tan L, Johnston C, Stark H. Cognitive improvements in children with Prader-Willi syndrome following pitolisant treatment—patient reports. J Pediatr Pharmacol Ther 2019;24(2):166-71. PMID 31019411
98: Qiu H, Liang X. Change in sleep latency as a mediator of the effect of physical activity intervention on executive functions among children with ADHD: a secondary analysis from a randomized controlled trial. J Autism Dev Disord 2023. [Epub ahead of print] PMID 37256478
99: Ramtekkar UP. DSM-5 changes in attention deficit hyperactivity disorder and autism spectrum disorder: implications for comorbid sleep issues. Children (Basel) 2017;4(8):62. PMID 28749421
100: Rigney G, Ali NS, Corkum PV, et al. A systematic review to explore the feasibility of a behavioural sleep intervention for insomnia in children with neurodevelopmental disorders: a transdiagnostic approach. Sleep Med Rev 2018;41:244-54. PMID 29764710
101: Robinson AM, Richdale AL. Sleep problems in children with an intellectual disability: parental perceptions of sleep problems, and views of treatment effectiveness. Child Care Health Dev 2004;30(2):139-50. PMID 14961866
102: Rocha NS, Correa RDESA, Dias ACM, Bueno CDF. Association between sleep pattern and pharmacological treatment in children with attention deficit disorder with hyperactivity: a systematic review. Rev Paul Pediatr 2023;41:e2022065. PMID 37255110
103: Rodriguez Lara F, Carnino JM, Cohen MB, Levi JR. Advances in the use of hypoglossal nerve stimulator in adolescents with Down syndrome and persistent obstructive sleep apnea-a systematic review. Ann Otol Rhinol Laryngol 2024;133(3):317-24. PMID 38062678
104: Rosenzweig I, Glasser M, Crum WR, et al. Changes in neurocognitive architecture in patients with obstructive sleep apnea treated with continuous positive airway pressure. EBioMedicine 2016;7:221-9. PMID 27322475
105: Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol 2011;53(9):783-92. PMID 21518346
106: Saletin JM, Koopman-Verhoeff ME, Han G, et al. Sleep problems and autism impairments in a large community sample of children and adolescents. Child Psychiatry Hum Dev 2022. [Epub ahead of print] PMID 36515855
107: Santos RA, Costa LH, Linhares RC, Pradella-Hallinan M, Coelho FMS, Oliveira GDP. Sleep disorders in Down syndrome: a systematic review. Arq Neuropsiquiatr 2022;80(4):424-43. PMID 35293557
108: Sarber KM, Howard JJM, Dye TJ, Pascoe JE, Simakajornboon N. Sleep-disordered breathing in pediatric patients with Rett syndrome. J Clin Sleep Med 2019;15(10):1451-7. PMID 31596210
109: Scantlebury A, Mcdaid C, Dawson V, et al. Non-pharmacological interventions for non-respiratory sleep disturbance in children with neurodisabilities: a systematic review. Dev Med Child Neurol 2018;60(11):1076-92. PMID 30058146
110: Shelton AR, Malow B. Neurodevelopmental disorders commonly presenting with sleep disturbances. Neurotherapeutics 2021;18(1):156-69. PMID 33403472
111: Smith ACM, Boyd KE, Brennan C, et al. Smith-Magenis syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 2022. PMID 20301487
112: Smith ACM, Morse RS, Introne W, Duncan WC Jr. Twenty-four-hour motor activity and body temperature patterns suggest altered central circadian timekeeping in Smith-Magenis syndrome, a neurodevelopmental disorder. Am J Med Genet A 2019;179(2):224-36. PMID 30690916
113: Spruyt K, Braam W, Curfs LM. Sleep in Angelman syndrome: a review of evidence. Sleep Med Rev 2018;37:69-84. PMID 28784434
114: Spruyt K, Braam W, Smits M, Curfs LM. Sleep complaints and the 24-h melatonin level in individuals with Smith-Magenis syndrome: assessment for effective intervention. CNS Neurosci Ther 2016;22(11):928-35. PMID 27743421
115: Stores G. Sleep and its disorders in children and adolescents with a neurodevelopmental disorder: a review and clinical guide. Cambridge: Cambridge University Press, 2014:79-158.
116: Surtees ADR, Oliver C, Jones CA, Evans DL, Richards C. Sleep duration and sleep quality in people with and without intellectual disability: a meta-analysis. Sleep Med Rev 2018;40:135-50. PMID 29754933
117: Tascini G, Dell'Isola GB, Mencaroni E, Di Cara G, Striano P, Verrotti A. Sleep disorders in Rett syndrome and Rett-related disorders: a narrative review. Front Neurol 2022;13:817195. PMID 35299616
118: Taylor MA, Schreck KA, Mulick JA. Sleep disruption as a correlate to cognitive and adaptive behavior problems in autism spectrum disorders. Res Dev Disabil 2012;33(5):1408-17. PMID 22522199
119: Tesfaye R, Wright N, Zaidman-Zait A, et al. Investigating longitudinal associations between parent reported sleep in early childhood and teacher reported executive functioning in school-aged children with autism. Sleep 2021;44(9):zsab122. PMID 33987680
120: Tropea D, Giacometti E, Wilson NR, et al. Partial reversal of Rett syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 2009;106(6):2029-34. PMID 19208815
121: Urbano GL, Tablizo BJ, Moufarrej Y, Tablizo MA, Chen ML, Witmans M. The link between pediatric obstructive sleep apnea (OSA) and attention deficit hyperactivity disorder (ADHD). Children 2021;8(9):824. PMID 34572256
122: Urquhart DS, Gulliver T, Williams G, Harris MA, Nyunt O, Suresh S. Central sleep-disordered breathing and the effects of oxygen therapy in infants with Prader-Willi syndrome. Arch Dis Child 2013;98(8):592-5. PMID 23761691
123: Van der Heijden KB, Smits MG, Van Someren EJ, Ridderinkhof KR, Gunning WB. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad Child Adolesc Psychiatry 2007;46(2):233-41. PMID 17242627
124: Vasey C, McBride J, Penta K. Circadian rhythm dysregulation and restoration: the Role of melatonin. Nutrients 2021;13(10):3480. PMID 34684482
125: Veatch OJ, Malow BA, Lee HS, et al. Evaluating sleep disturbances in children with rare genetic neurodevelopmental syndromes. Pediatr Neurol 2021;123:30-7. PMID 34388423
126: Veatch OJ, Pendergast JS, Allen MJet al. Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay. J Autism Dev Disord 2015;45(1):100-10. PMID 25059483
127: Vermeulen K, Staal WG, Janzing JG, van Bokhoven H, Egger JIM, Kleefstra T. Sleep disturbance as a precursor of severe regression in Kleefstra syndrome suggests a need for firm and rapid pharmacological treatment. Clin Neuropharmacol 2017;40(4):185-8. PMID 28622207
128: Vetrini F, McKee S, Rosenfeld JA, et al. De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome. Genome Med 2019;11(1):12. PMID 30819258
129: Vgontzas AN, Bixler EO, Kales A, et al. Daytime sleepiness and REM abnormalities in Prader-Willi syndrome: evidence of generalized hypoarousal. Int J Neurosci 1996;87(3-4):127-39. PMID 9003974
130: Vitrikas K, Dalton H, Breish D. Cerebral palsy: an overview. Am Fam Physician 2020;101(4):213-20. PMID 32053326
131: Weaving LS, Ellaway CJ, Gécz J, Christodoulou J. Rett syndrome: clinical review and genetic update. J Med Genet 2005;42(1):1-7. PMID 15635068
132: Wile I. Physical problems of abnormal behavior. Am J Dis Child 1928;35(1):113-9.
133: Williams PG, Sears LL, Allard A. Sleep problems in children with autism. J Sleep Res 2004;13(3):265-8. PMID 15339262
134: Williams SR, Zies D, Mullegama SV, Grotewiel MS, Elsea SH. Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity. Am J Hum Genet 2012;90(6):941-9. PMID 22578325
135: Wynchank D, Bijlenga D, Beekman AT, Kooij JJS, Penninx BW. Adult attention-deficit/hyperactivity disorder (ADHD) and insomnia: an update of the literature. Curr Psychiatry Rep 2017;19(12):98. PMID 29086065
136: Xiong M, Li F, Liu Z, et al. Efficacy of melatonin for insomnia in children with autism spectrum disorder: a meta-analysis. Neuropediatrics 2023;54(3):167-73. PMID 36827993
137: Yee BJ, Buchanan PR, Mahadev S, et al. Assessment of sleep and breathing in adults with Prader-Willi syndrome: a case control series. J Clin Sleep Med 2007;3(7):713-8. PMID 18198805
138: Yenen AS, Cak HT. Melatonin and circadian rhythm in autism spectrum disorders. Turk Psikiyatri Derg 2020;31(3):201-11. PMID 32978956
139: Young D, Nagarajan L, de Klerk N, Jacoby P, Ellaway C, Leonard H. Sleep problems in Rett syndrome. Brain Dev 2007;29(10):609-16. PMID 17531413

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Katelyn Bricker MD MS

Dr. Bricker of the University of North Carolina has no relevant financial relationships to disclose.
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Bradley V Vaughn MD

Dr. Vaughn of UNC Hospital Chapel Hill and University of North Carolina School of Medicine has no relevant financial relationships to disclose.
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Former Authors

Michael W Naylor MD
John Garcia MD
Stephen P Duntley MD
Michael J Rack MD
K K Jain MD†
Antonio Culebras MD FAAN FAHA FAASM

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Autistic disorder: 299.0

Down syndrome: 758.0

Intellectual disability: 317-9

Prader-Willi syndrome: 759.81

Rett syndrome: 330.8
ICD-10: Childhood autism: F84.0

Down syndrome: Q90

Intellectual disability: F70-9

Prader-Willi syndrome: Q87.1

Rett syndrome: F84.2
OMIM: Autism: %209850

Down syndrome: #190685

Prader-Willi syndrome: #176270

Rett syndrome: #312750

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Sleep and intellectual disability

Associated Disorders

Down syndrome
Prader-Willi syndrome

Differential Diagnosis

brain and brainstem dysfunction involved in sleep-wake regulation
circadian rhythm disorder
central sleep apnea
obstructive sleep apnea
nocturnal seizures
- poor sleep hygiene
- psychosocial factors
- medications

Also Relevant

Angelman syndrome
Autism spectrum disorder
Down syndrome
Intellectual disability
Irregular sleep-wake rhythm disorder
- Obstructive sleep apnea
- Prader-Willi syndrome
- Rett syndrome
- Sleep disorders
- Sleep and medical disorders

Sleep and intellectual disability

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Table 1. Sleep Disorder Etiology by Disorder

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Sleep-related breathing disorders

Sleep apnea and hypoventilation

Special considerations

Anesthesia

References

Contributors

Authors

Former Authors

Patient Profile

ICD & OMIM codes

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Questions or Comment?

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