Atypical Sleep Architecture in Children with 15q11.2-13.1 Duplication (Dup15q) Syndrome (4436)

Objective: To examine sleep physiology in children with Dup15q syndrome, with focus on oscillatory power, sleep spindle density and slow wave sleep, and to compare these features to those in typically developing children.

Background: Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for intellectual disability, autism, hypotonia and epilepsy. Genes in the 15q region, particularly UBE3A and a cluster of GABA_A receptor genes, are critical for neural development, disrupting synaptic protein synthesis and degradation as well as inhibitory neurotransmission. Children with Dup15q syndrome have increased beta oscillations (12–30 Hz) during wakefulness that likely reflect aberrant GABAergic neurotransmission, and studies have shown that non-REM sleep rhythms are also highly dependent on GABAergic neurotransmission. Healthy sleep physiology is necessary for robust cognitive development, yet no studies to date have quantified NREM sleep physiology parameters in children with Dup15q syndrome.

Design/Methods: 7 hours of overnight sleep EEG recording from a cohort of children with Dup15q syndrome (n=15, mean age: 5.7 years) and age-matched neurotypical controls (n=12, mean age: 5.8 years) were analyzed. Beta power in sleep, spindle density and percentage of slow wave sleep (SWS) were computed and compared between groups.

Results: Compared to typically developing, age-matched controls, children with Dup15q syndrome showed significantly elevated beta power in sleep (frontal: p=0.001, central: p=0.01 and occipital: p=0.0009 channels), reduced spindle density (p<0.0001) and reduced or sometimes absent SWS (frontal: p<0.0001, central: p=0.0003 and occipital: p=0.0005 channels).

Conclusions: Here, we have quantified sleep physiology in children with a genetic syndrome highly penetrant for epilepsy and neurodevelopmental disabilities. Insights from this study promotes a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome and lays the foundation for studies that investigate relationship between sleep and cognition. Abnormal sleep physiology may undermine cognitive development in Dup15q syndrome and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions.

Disclosure: Miss Saravanapandian has nothing to disclose. Dr. Nadkarni has nothing to disclose. Dr. Hussain has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MGC Pharma. Dr. Hussain has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zogenix. Dr. Hussain has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Grenwich Biosciences. An immediate family member of Dr. Maski has received personal compensation for serving as an employee of Sanofi Genzyme. Dr. Maski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony Biosciences. Dr. Maski has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alkermes. An immediate family member of Dr. Maski has received stock or an ownership interest from Sanofi Genzyme. The institution of Dr. Maski has received research support from Jazz Pharmaceuticals. The institution of Dr. Maski has received research support from NIH 5K23NS104267-2. The institution of Dr. Maski has received research support from Coverys. Dr. Maski has received publishing royalties from a publication relating to health care. Dr. Jeste has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN Continuum. The institution of Dr. Jeste has received research support from NIH. The institution of Dr. Jeste has received research support from DoD. The institution of Dr. Jeste has received research support from Dup15q Alliance.