Sleep disturbances in Angelman syndrome: a questionnaire study

Abstract

Only few studies are available on sleep disorders in Angelman syndrome (AS), a neurodevelopmental disorder with several behavior disturbances. The aim of this study was to determine the prevalence of sleep disorders in a relatively large group of AS subjects, compared to that of age-matched controls. Fourty-nine consecutive parents of patients with AS (26 males and 23 females aged 2.3–26.2 years) were interviewed and filled out a comprehensive sleep questionnaire. Based on their genetic etiology, four groups were defined: deletion of chromosome 15q11–13 (25 subjects); methylation imprinting mutation (six subjects), UBE3A mutations (seven subjects) and paternal uniparental disomy (five subjects). In the remaining cases genetic testings were negative. A significantly high frequency of disorders of initiating and maintaining sleep, prolonged sleep latency, prolonged wakefulness after sleep onset, high number of night awakenings and reduced total sleep time were found in our AS patients, as compared to age-matched controls. We also found other types of sleep disorders, never reported before, such as enuresis, bruxism, sleep terrors, somnambulism, nocturnal hyperkinesia, and snoring. No differences were found between the four genetic aetiology groups. Moreover, we did not find important improvement of sleep disturbances from pre-pubertal to post-pubertal ages. Our data confirm the significant presence of sleep/wake rhythms fragmentation, peculiar of AS, and also demonstrate the presence of several other types of sleep disturbances in this syndrome.

Introduction

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation, severe speech impairment, ataxia of gait and/or tremulous movement of limbs, specific behavioral traits – such as frequent laughter, jerky (puppet-like) movements – microcephaly, abnormal EEG features, epilepsy and dysmorphic cranio-facial features. A consensus for diagnostic criteria was established in 1995, the symptoms and/or signs listed above are present in approximately 80–100% of cases [1]. The prevalence of AS is estimated to be around 1:10,000–1:20,000 and the clinical diagnosis can be confirmed by cytogenetic or DNA testing in 80–85% of cases while in 15–20% of subjects the etiology is still unknown [2].

Sleep problems such as sleep/wake rhythm disorders, multiple nocturnal awakenings, or difficulties in falling asleep are known to be frequent in AS [1] but have not been assessed by means of specific tools for their detection. Instead, they have been found using questionnaires built for the assessment of other behavioral features [3], [4], [5], [6], [7].

There are also indications that sleep might show an age-related improvement in AS because Smith [4] studied an Australian sample of 21 patients and found that their previous sleep problems had disappeared in a large percentage (75%) at follow up, 10 years later. Moreover, a recent report has shown an increase in total sleep time and improvement in sleep quality in adolescents and adults with AS [7]; the same authors suggested that some developmental factors, probably linked to cerebral plasticity, might be responsible for both the early sleep-wake disruption and for its improvement with age.

The main scope of our study was to determine the prevalence of sleep disorders in a relatively large group of subjects with AS, in comparison with that found in age-matched healthy controls, by means of a questionnaire specifically arranged for the study of sleep characteristics of children and adolescents and already validated [8]; moreover, our aim was also to assess the eventual presence of specific sleep disorders in AS and to confirm or not their age-related improvement already reported in the literature [4], [7].