Endocrine and neurophysiological examination of sleep disorders in Williams syndrome

Background: A high rate of sleep disturbances have been reported in individuals with Williams syndrome (WS), but the underlying aetiology has yet to be identified. Melatonin and cortisol levels are known to affect and regulate sleep/wake patterns. We investigated the changing levels of these hormones in order to explore any relationship with sleep disturbances in children with WS.
Methods: Twenty seven children with WS and 27 typically developing (TD) children were recruited. Sleep was monitored using actigraphy and pulse oximetry. Parents completed Children’s Sleep Habit Questionnaire (CSHQ). Saliva and first void morning urine samples were collected from the children. Saliva was collected at three time points: 4-6pm, before bedtime and first thing after awakening. Levels of salivary melatonin and cortisol were analysed by enzyme linked immunoassays. For determination of melatonin, cortisol and their metabolites in urine samples, specific Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed.
Results: CSHQ and actigraphy indicated that children with WS were significantly affected by several types of sleep disturbances, including: abnormally high sleep latency and excessive night waking. Children in WS group had shallower falls in salivary cortisol levels and less pronounced rises in salivary melatonin at bedtime compared to TD controls (p < 0.01 and p = 0.04 respectively). Furthermore, it was found that children with WS also had significantly higher levels of bedtime cortisol compared to TD controls (p = 0.03). Using UHPLC-MS/MS analysis it was shown that children with WS secrete less melatonin during the night compared to healthy controls (p < 0.01). Also, levels of cortisone, a metabolite of cortisol were significantly higher in the WS group (p = 0.05).
Conclusions: We found that children with WS had significant sleep disturbances which may be associated with their increased bedtime cortisol and lower evening melatonin. Both hormones play a significant role in the circadian rhythm and sleep/wake cycle, therefore it was necessary to look closely at these endocrine markers in individuals suffering from sleep disorders. Sleep problems in children with WS may adversely affect daytime activity and the quality of life, as well as social, emotional, health and economic functioning of the entire family. Hence, finding their cause is of great importance for affected children and their families.