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Wadih M. Zein, John A. Butman, Tanya J. Lehky, Stephen J. Sharp, Tracy L. Levy, Jennifer C. Hanowell, Jack W. Tsao, Kristen E. Bowles, Brian P. Brooks, Joan C. Han; Duane Syndrome in WAGR Patients with CGH-defined Deletions of 11p and Neuroradiologic Absence of the Abducens Nerve. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1587.
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WAGR syndrome (Wilms tumor, aniridia, genitourinary abnormalities, mental retardation) is caused by heterozygous contiguous gene deletions in chromosome 11p13 region; patients with changes in that region show multiple ocular and neurodevelopmental abnormalities. We report three patients with WAGR syndrome who demonstrate ophthalmic and magnetic resonance imaging (MRI) signs of Duane syndrome.
29 patients (age 6-37y) with WAGR syndrome underwent ophthalmic examination and MRI as part of a comprehensive phenotype-genotype correlation study. Peripheral nerve conduction studies were performed as part of a neurologic assessment. The patients also had precise localization of the causative deletions on the 11p chromosome by means of array comparative genomic hybridization (CGH).
3 patients (12yo male, 16 and 28yo females) with WAGR syndrome showed evidence of limitation of abduction of the left eye on ophthalmic examination. Visual acuity ranged from 20/150 to 20/500; one patient had a right ocular prosthesis. MRI showed hypoplasia or absence of the left abducens nerve in all three of these patients. Peripheral motor and sensory nerve conduction studies were normal. All three patients had de novo chromosome 11p13 deletions (size 8.97-13.47 Mb) with a shared deletion region of 5.34 Mb (Chr11:30,861,844 to 36,203,063) that encompasses 20 known genes in common, including PAX6, WT1, PRRG4, and SLC1A2.
We report an association of unilateral Duane syndrome in three patients with WAGR syndrome. These findings suggest that a gene within this 11p13 critical region - in addition to those mapped/cloned on chromosomes 8q, 2q (CHN1), and 20q (SALL4, Duane-radial ray syndrome) - may be important in the pathogenesis of Duane syndrome. Rodent model evidence points to the importance of Pax6, one of the genes in the 11p13 region, in regional brain differentiation. Previously published detailed MRI studies of patients with PAX6 mutations failed to demonstrate anatomical lesions of the abducens nerve, leaving the door open for the possibility of involvement of other genes in the deleted region.
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