Objective: PAX6 haploinsufficiency ( +/-) can occur due to mutations involving only PAX6 in patients with isolated aniridia or as contiguous gene deletions in patients with Wilms tumor, aniridia, genitourinary anomalies, and range of developmental and intellectual disabilities syndrome. Given the role of PAX6 in pineal development and circadian regulation, adolescents with PAX6+/- may experience sleep-wake disturbances. The purpose of this observational study was to explore sleep-related phenotypes in adolescents with PAX6+/-.
Methods: This study compared sleep phenotypes of nine subjects with PAX6+/- (aged 10-19 years) with previously published data on healthy adolescents ( n = 25, aged 10-18 years). Subjects completed the Cleveland Adolescent Sleepiness Questionnaire (CASQ), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b) Questionnaires and wore actigraphs for seven nights to record sleep patterns.
Results: Total CASQ, PROMIS sleep-related impairment, and PROMIS sleep disturbance scores were not statistically different between the groups ( ps > .15). Actigraph data for lights off to sleep-onset time were found to be significantly higher in subjects with PAX6+/- versus the healthy comparison group (adjusted mean [95% confidence interval]: 20.1 min [8.1, 49.8] vs. 6.2 min [3.7, 10.4], respectively, p = .04).
Conclusion: Both adolescents with PAX6+/- and the healthy comparison group on average slept less than 8 hr/night, and overall sleep deprivation in adolescents may have masked differences between groups. This study used rare genetic disorders with biological vulnerability to sleep problems as a genotype-phenotype model. Knowledge of sleep-related phenotypes will assist in designing studies to manage sleep-related symptoms in adolescents.
Keywords: CASQ; PAX6; PROMIS; actigraphy; adolescence; sleep.