Skip to main content

PAX6 haploinsufficiency: pineal hypoplasia, reduced melatonin, & sleep disturbance

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • A.E. Hanish
  • J.A. Butman
  • F. Thomas
  • J. Yao
  • A.E. Huey
  • M.D. Lee
  • E. Yin
  • L.A. Hunter
  • M.D. Hicks
  • T. Singh
  • M. Tsang
  • J.C. Han


Background: PAX6 haploinsufficiency (PAX6 +/-) is associated with aniridia and can occur as part of contiguous gene deletion syndrome (WAGR) or as mutations and microdeletions affecting only PAX6. In addition to its role in eye development, PAX6 may also play an important role in the development of the pineal, a gland in the brain that produces melatonin, a hormone involved in circadian regulation. Pineal hypoplasia has been previously reported in subjects with PAX6 +/-; however melatonin and sleep have not been assessed. Methods: 39 WAGR subjects, 13 PAX6+/- subjects, and 20 controls were evaluated as inpatients. Pineal was evaluated by brain MRI. Serum melatonin and urine 6-sulfatoxymelatonin (6SM) were measured by ELISA. The Child Sleep Habits Questionnaire (CSHQ) was administered for subjects <13y. Results: Pineal volume was 6-fold lower in PAX6 +/- (n=20) vs. controls (n=16, p<0.001). Midnight serum melatonin was 2.5-fold lower in PAX6 +/- (n=28) vs. controls (n=18, p<0.001). First morning void 6SM was 4-fold lower in PAX6 +/- (n=27) vs. controls (n=18, p<0.001). CSHQ score was 11% higher in PAX6 +/- (n=28) vs. controls (n=15, p=0.03). Conclusions: Our findings suggest that PAX6+/- is associated with smaller pineal size, lower melatonin secretion, and greater sleep disturbances in children.

back to top