Angelman syndrome (AS) is characterized by severe intellectual, speech and motor deficits [1]. The cause of AS is either disruption of the maternal ubiquitin-protein ligase E3A gene (UBE3A) (30%) or deletion of chromosome 15 at 15q11-q13 (70%). The deleted region includes UBE3A and GABRB3, GABRA5, and GABRG3, genes that encode the gamma-aminobutyric acid (GABA) type A receptor subunits β3, α5, and γ3. Several medical co-morbidities are associated with AS.

Sleep disturbance is a common medical co-morbidity, occurring in up to 80% of individuals with AS. Difficulty falling and staying asleep and reduced total sleep time are most common. The etiology of sleep disturbances in AS is multifactorial, involving genetic, co-morbid medical, and behavioral factors. Deletion of the GABRB3-GABRA5-GABRG3 gene grouping, which occurs in most cases of AS, probably contributes to the high prevalence of sleep problems and co-morbid epilepsy [2]. Epilepsy occurs in 80–90% of individuals with AS and can contribute to sleep problems. In a study of sleep disturbances and epilepsy in 290 subjects with AS, disturbed sleep was described by caregivers of 58% of the sample [3]. Among these subjects, 79% had epilepsy, and 69% of those with both sleep problems and epilepsy had multiple seizure types. Subjects with epilepsy non-responsive to more than two antiepileptic drugs (AEDs) had more significant sleep disturbances than those successfully treated with up to two AEDs. From a behavioral standpoint, urinary incontinence overnight may cause mid-nocturnal awakenings, and agitation in response to separation from preferred caregivers may play a role in the disturbed sleep.

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