Familial advanced sleep phase syndrome

Background: The circadian rhythms of sleep propensity and melatonin secretion are regulated by a central circadian clock, the suprachiasmatic nucleus of the hypothalamus. The most common types of sleep disorders attributed to an alteration of the circadian clock system are the sleep/wake cycle phase disorders, such as delayed sleep phase syndrome and advanced sleep phase syndrome (ASPS). Advanced sleep phase syndrome is characterized by the complaint of persistent early evening sleep onset and early morning awakening. Although the complaint of awakening earlier than desired is relatively common, particularly in older adults, extreme advance of sleep phase is rare. Objective: To phenotypically characterize a familial case of ASPS. Methods: We identified a large family with ASPS; 32 members of this family gave informed consent to participate in this study. Measures of sleep onset and offset, dim light melatonin onset, the Horne-Ostberg morningness-eveningness questionnaire, and clinical interviews were used to characterize family members as affected or unaffected with ASPS. Results: Affected members rated themselves as "morning types" and had a significant advance in the phase of sleep onset (P < .001) and offset (P = .006) times. The mean sleep onset was 2121 hours for the affected family members and 0025 hours for the unaffected family members. The mean sleep offset was 0507 hours for the affected members and 0828 hours for the unaffected members. (Times are given in military form.) In addition, the phase of the circadian rhythm of melatonin onset for the affected family members was on average 3 1/2 hours earlier than for the unaffected members. Conclusions: The ASPS trait segregates with an autosomal dominant mode of inheritance. The occurrence of familial ASPS indicates that human circadian rhythms, similar to those in animals, are under genetic regulation. Genetic analysis of familial sleep and circadian rhythm disorders is important for identifying a specific gene(s) responsible for the regulation of sleep and circadian rhythms in humans.