Table 1.

Sleep and translation phenotypes are shared across many genetically distinct NDDs and likely contribute to synaptic and cognitive phenotypes

	Prevalence of sleep deficits	Sleep phenotypes	Translational phenotypes	Synaptic phenotypes	Cognitive and behavioral phenotypes
Autism spectrum disorder	86% (Liu et al. 2006)	Insomnia, bedtime resistance, parasomnias, sleep disordered breathing, morning rise problems, daytime sleepiness, increased sleep latency, decreased sleep efficiency, decreased REM, increased late-stage NREM (Liu et al. 2006)	Dysregulated translation (variable) (Lu and Hsueh 2021)	Abnormal mGluR5-mediated synaptic plasticity, increased dendritic spine density (variable, decreased in some models) (Nishiyama 2019)	Restrictive and repetitive behaviors, avoiding physical contact, communication deficits, sometimes non-verbal, social interaction deficits (Saxena and Chahrour 2017)

Fragile X syndrome

32–77% (Kronk et al. 2010; Richdale 2003)

Increased sleep latency, sleep fragmentation, reduced REM duration, fewer REM bouts, disrupted NREM (Kronk et al. 2010; Miano and Ferri 2010)

Enhanced or repressed translation depends on transcript features (Darnell et al. 2011; Greenblatt and Spradling 2018)

Overabundant dendritic spines, immature spines with long, thin morphology, excessive glutamate receptor internalization, enhanced mGluR-dependent LTD (Hodges et al. 2017)

Cognitive impairment, hyperactivity, anxiety, social avoidance, hyperarousal to stimuli, attention deficits, increased risk of ASD (Lozano et al. 2014)

Rett syndrome

80% (Boban et al. 2018)

Increased sleep latency, nighttime waking, fragmented sleep, impaired sleep rebound, sleep apnea, excessive daytime sleepiness, increased total sleep time, abnormal REM/NREM rhythm (Boban et al. 2018)

Reduced global translation (Rodrigues et al. 2020)

Decreased dendritic spine density, impaired dendritic arborization (Lo and Lai 2020)

Regression of learned abilities, epileptic seizures, impaired nociception, stereotypic hand movements, poor response to environmental stimulation, impaired cognitive, social, and motor skills (Nomura 2005)

Down syndrome

65% (90% sleep apnea) (Horne et al. 2019)

Sleep apnea, increased sleep latency, frequent night awakening, parasomnias, fragmented sleep, reduced REM, daytime sleepiness, decreased sleep efficiency, decreased NREM stage 2 (Horne et al. 2019; Heubi et al. 2021)

Disrupted proteostasis through activation of the integrated stress response (ISR) translational pathway (Zhu et al. 2019)

Reduced spine density, larger dendritic spine heads, reduced cortical dendritic branching, spine maturation deficits, impaired synaptogenesis (Lauterborn et al. 2020)

Impaired memory, hyperactivity, intellectual disability, increased risk of Alzheimer's disease, delayed expressive language and verbal deficits, decreased anxiety, impaired attention, perception, and motor skills, sensory impairment, seizures (Grieco et al. 2015)