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J. L. Demer, R. A. Clark, M. A. Tischfield, E. C. Engle; Magnetic Resonance Imaging (MRI) Evidence of an Asymmetrical Endophenotype in Congenital Fibrosis of Extraocular Muscles Type 3 Due to TUBB3 Mutation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4762.
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Orbital magnetic resonance imaging (MRI) was employed to investigate the structural basis of ocular motility abnormalities congenital fibrosis of the extraocular muscles type 3 (CFEOM3), a disorder resulting from missense mutations in TUBB3, encoding the neuron-specific β-tubulin isotype III.
Clinical ophthalmic findings in 10 affected and three related but clinically unaffected volunteers from four CFEOM3 pedigrees, and normal controls, were correlated with MRI demonstrating extraocular muscle (EOM) size, location, contractility, and innervation. Coronal T1 weighted MRI scans of the orbits were obtained using surface coils in multiple gaze positions at 2 mm thickness (234-312 micron resolution), as well as oblique heavily T2 weighted images in the plane of the cranial nn. at 1 mm thickness (390 micron resolution). MRI findings were correlated with motility examinations.
Subjects with CFEOM3 had frequently asymmetrical blepharoptosis, limited vertical duction, variable ophthalmoplegia, exotropia, and frequently paradoxical abduction in infraduction. In affected subjects, MRI demonstrated variable, asymmetrical levator palpebrae superioris and superior rectus EOM atrophy correlating with blepharoptosis and deficient supraduction, and small orbital motor nerves. While at least one oculomotor nerve (CN3) was hypoplastic, ophthalmoplegia was present only when subarachoid CN3 width was less than 1.9 mm. Multiple EOMs exhibited variable hypoplasia, correlating with duction in individual orbits. A-pattern exotropia was frequent correlating with lateral rectus (LR) muscle misinnervation by CN3. Optic nerve (ON) cross sections were subnormal, but rectus pulley locations were normal.
CFEOM3 features asymmetrical abnormalities of motor innervation and EOM function correlating with the degree of subarachoid CN3 hypoplasia, and subclinical ON hypoplasia resembling CFEOM1. Frequent LR innervation by the inferior rectus motor branch of CN3 is a feature overlapping with Duane retraction syndrome. These findings suggest that CFEOM3 is an asymmetrical, variably penetrant congenital cranial dysinnervation disorder leading to secondary myopathy.
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