RESUMO
Smith-Magenis syndrome (SMS) is a contiguous gene syndrome linked to interstitial microdeletion, or mutation of RAI1, within chromosome 17p11.2. Key behavioral features of SMS include intellectual disability, sleep-disturbances, maladaptive, aggressive and self-injurious behaviors, hyperactivity, and sudden changes in mood. A distinguishing feature of this syndrome is an inverted pattern of melatonin characterized by elevated daytime and low nighttime melatonin levels. As the central circadian clock controls the 24-hr rhythm of melatonin, we hypothesized that the clock itself may contribute to the disrupted pattern of melatonin and sleep. In this report, 24-hr patterns of body temperature, a surrogate marker of clock-timing, and continuous wrist activity were collected to examine the links between body temperature, sleep behavior, and the circadian clock. In addition, age-dependent changes in sleep behavior were explored. Actigraphy-estimated sleep time for SMS was 1 hr less than expected across all ages studied. The timing of the 24-hr body temperature (Tb-24) rhythm was phase advanced, but not inverted. Compared to sibling (SIB) controls, the SMS group had less total night sleep, lower sleep efficiency, earlier sleep onset, earlier final awake times, increased waking after sleep onset (WASO), and increased daytime nap duration. The timing of wake onset varied with age, providing evidence of ongoing developmental sleep changes from childhood through adolescence. Clarification of the circadian and developmental factors that contribute to the disrupted and variable sleep patterns in this syndrome will be helpful in identifying more effective individualized treatments.