Abstract:

 Objective To identify the clinical phenotype and MRI manifestation of congenital fibrosis of extraocular muscles (CFEOM) with different TUBB3 gene mutations. Design Retrospective case series. Participants Seven CFEOM patients with four different TUBB3 gene mutations (p.R262C, p.R262H, p.R380C, p.E410K) in Beijing Tongren Hospital from Mar 2013 to Apr 2018 were involved. Methods The clinical data and magnetic resonance imaging(MRI) of the ocular motor nerves and brain were collected for comparative analysis according to the difference of TUBB3 gene mutations. Main Outcome Measures Ocular examination results, physical examination results, MRI of the ocular motor nerves and brain. Results All the patients with TUBB3 mutations showed typical CFEOM phenotype, Neuroimaging reveals hypoplasia of oculomotor nerves and the atrophy of corresponding extraocular muscles. Thereinto, CFEOM was the only abnormality in patients with R262C mutation; patients with R262H, R380C and E410K mutation had mild to moderate intellectual, behavioral and movement impairments, common finding of brain imaging were dysgenesis of the corpus callosum; individuals with R262H also had multiple limb abnormalities, including congenital finger contracture, funnel chest and coxa valga etc. Conclusion TUBB3 gene mutations are one of the leading causes of Chinese CFEOM patients, different mutations in TUBB3 gene correspond to different clinical phenotypes. Genotype-phenotype association could assist clinical diagnosis and phenotyping. (Ophthalmol CHN, 2018, 27: 276-280)

Key words: congenital fibrosis of extraocular muscles, TUBB3 gene, phenotype, MRI