Background: The circadian rhythms of sleep propensity and melatonin secreti
on 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 s
yndrome (ASPS). Advanced sleep phase syndrome is characterized by the compl
aint of persistent early evening sleep onset and early morning awakening. A
lthough the complaint of awakening earlier than desired is relatively commo
n, 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-eveni
ngness questionnaire, and clinical interviews were used to characterize fam
ily members as affected or unaffected with ASPS.
Results: Affected members rated themselves as "morning types" and had a sig
nificant 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 wa
s 0507 hours for the affected members and 0828 hours for the unaffected mem
bers. (Times are given in military form.) In addition, the phase of the cir
cadian rhythm of melatonin onset for the affected family members was on ave
rage 31/2 hours earlier than for the unaffected members.
Conclusions: The ASPS trait segregates with an autosomal dominant mode of i
nheritance. 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.