Advanced sleep phase syndrome

Overview
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 the University of California, San Francisco 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.

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 and mouse models, which produced short-day mutants and were predicted to produce a phase advance in humans. 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.

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. The evidence for both of these reported causes of FASPS is strengthened by the absence of said mutations in all tested control subjects.