Pineal hypoplasia and decreased melatonin in patients with PAX6 haploinsufficiency due to WAGR syndrome or PAX6 mutations

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NICHD	ENDOC-6

Authors

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

Abstract

Background: Aniridia can be caused by isolated PAX6 haploinsufficiency (+/-) due to mutations or heterozygous deletion as part of WAGR/11p deletion syndrome. Pineal gland hypoplasia has been previously reported, but melatonin has not been studied in humans with PAX6 mutations. 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: The prevalence of pineal gland hypoplasia was higher in WAGR (58%) and PAX6+/- (45%) vs. controls (0%, p<0.01). Midnight melatonin was ~2-fold lower in WAGR and PAX6+/- vs. controls (p<0.01). Midnight melatonin was ~2-fold lower in those with vs. without pineal hypoplasia (p=0.02). Morning urinary 6SM level (reflecting nighttime production) was ~4-fold lower in WAGR and PAX6+/- as compared to controls (p<0.01). CSHQ score was ~30% higher for WAGR/PAX6+/-vs. controls, but not statistically different (p=0.08). Conclusions: Pineal hypoplasia occurred in 55% of WAGR/PAX6+/- subjects, and was associated with lower melatonin production. In WAGR/PAX6+/- children, there was a trend toward greater sleep disturbance. Our findings support the view that PAX6 plays an important role in pineal development and function.

back to top