SMS & Sleep Disturbance

One of the most common symptoms of SMS is a severe sleep disorder associated with significant disruptions in the lives of patients and their families ^4-5

The sleep disturbances that occur in affected individuals is a chronic lifelong problem, and is the strongest predictor of maladaptive behavior.

Sleep disturbances in patients with SMS include difficulty falling asleep, frequent nighttime awakenings, early wake times, reduced total sleep time at night, and daytime sleepiness^4-6

The sleep abnormalities are associated with an inverted circadian rhythm of melatonin, reported in over 90% of cases. In most people, levels of the hormone melatonin increase in the evening and peak in the late night, during sleep.9 In nearly all patients with SMS this rhythm is altered, marked by lower melatonin levels that peak during the day^10-12

Altered and/or diminished pattern of melatonin secretion in patients with SMS may be the result of a dysfunctional internal circadian clock, most likely due to loss of the RAI1 gene^13,14

References:
(1) Elsea, S. H. & Girirajan, S. Eur.J Hum Genet. 16, 412–421 (2008). (2) Greenberg, F. et al. Am J Hum Genet. 49, 1207–1218 (1991). (3) Smith, A. C., Magenis, R. E. & Elsea, S. H. J Assoc.Genet.Technol. 31, 163–167 (2005). (4) Foster, R.H. et al. J. Genet. Couns. 19, 187–198 (2010). (5) Shayota, B. J. & Elsea, S. H. Curr. Opin. Psychiatry 32, 73–78 (2019). (6) Nag, H. E., Hoxmark, L. B. & Nærland, T. J. Intellect. Disabil. 23, 359–372 (2019). (7) Trickett, J. et al. Sleep. 43(4):1–26 (2020). (8) Gropman, A.L., Duncan, W.C., Smith, A.C. Pediatr Neurol. May; (34) 337–50 (2006). (9) Dawson, D. & Van Den Heuvel, C. J. Ann. Med. 30, 95–102 (1998).
(10) De Leersnyder, H. et al. J. Pediatr. 139, 111–116 (2001). (11) Potocki, L. et al. J. Med. Genet. 37, 428–33 (2000). (12) Spruyt, K. et al. CNS Neurosci. Ther. (2016). (13) De Leersnyder, H. Trends Endocrinol Metab 17, 291–298 (2006). (14) Williams, S.R. et al. Am. J. Hum. Genet. 90, 941–949 (2012).