Advanced sleep phase syndrome

Advanced sleep phase syndrome (ASPS) is a sleep disorder in which patients feel very sleepy early in the evening (e.g. 18:00-19:00) and wake up very early in the night (e.g. midnight, 1:00, etc.).

It is the opposite of delayed sleep phase syndrome.

ASPS is frequently encountered in the elderly and in post-menopausal women. It can be treated pharmacologically, with evening bright lights, or behaviorally with chronotherapy or free-running sleep.

Familial advanced sleep phase syndrome (FASPS') In 1999, Louis Ptáček’s research group at UCSF reported findings of a human circadian rhythm disorder showing a familial tendency. The disorder was characterized by a life-long pattern of sleep onset around 7:30pm and offset around 4:30am. Among three lineages, 29 people were identified as affected with this familial advanced sleep-phase syndrome (FASPS), and 46 were considered unaffected. The pedigrees demonstrated FASPS to be a highly penetrant, autosomal dominant trait (Jones et al 1999).

Two years after reporting the finding of FASPS, Ptáček’s group published results of genetic sequencing analysis on a family with FASPS. To narrow their search they took a cue from research on Per mutations in Drosophila (Konopka 1971) and mouse (Zehng 1999) models, which produced short-day mutants and were predicted to produce a phase advance in humans (Klerman 1996). With this guidance they quickly found what they were looking for. Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CK1ε binding domain of the hPER2 protein (Toh et al 2001).

In 2005, Ptáček’s lab reported discovery of a different mutation causing FASPS. This time the CK1δ was implicated, demonstrating an A-to-G missense mutation that resulted in a threonine-to-alanine alteration in the protein (Xu et al 2005). The evidence for both of these reported causes of FASPS is strengthened by the absence of said mutations in all tested control subjects (Toh et al 2001: Xu et al 2005).

References

Jones, CR et al. 1999. Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans. Nature Med. 5:9, 1062-1065.

Klerman, EB et al. 1996. Simulations of light effects on the human circadian pacemaker: implications for assessment of intrinsic period. Am. J. Physiol. 270:39, 271-282.

Konopka, RJ, and Benzer, S. 1971. Clock Mutants of Drosophila melanogaster. Proc. Nat. Acad. Sci.. 68:9, 2112-2116.

Toh, KL et al. 2001. An hPer2 Phosphorylation Site Mutation in Famial Advanced Sleep Phase Syndrome. Science. 291, 1040-1043.

Xu, Y et al. 2005. Functional Consequences of a CK1δ Mutation Causing Familal Advanced Sleep Phase Syndrome. Nature. 434, 640-644.

Zehng, B et al. 1999. The mPer2 gene encodes a functional component of the mammalian circadian clock. Nature. 400, 169-173.