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yuan wang, Jingjing Jiang, Jingyuan Zhu, xueqing Bai, LIjuan Huang, Hui Li, Ningdong Li; Clinical and genetic analysis for the Chinese patients with CCDDs. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4444.
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Congenital Cranial Disinnervation Disorders (CCDDs) refers to a group of complex ocular motility disorders with clinical and genetic heterogeneity. It comprises of Congenital Fibrosis of Extraocular Muscles (CFEOM), Duane Retraction Syndrome (DRS), Mobius Syndrome (MS) and Horizontal Gaze Palsy with Progressive Scolosis (HGPPS). In this study, we analyze the clinical features of 23 families with CFEOM, 5 families and 17 affected individuals with DRS, 13 sporadic affected individuals with MS, and 1 family with HGPPS. We also investigate the gene mutations of KIF21A, Tubb3, CHN1, and Robo3 gene mutations in affected individuals CCDDs.
We retrospectively reviewed the medical records of 23 families with CFEOM, 5 families and 17 affected individuals with DRS, 13 sporadic affected individuals with MS, and 1 family with HGPPS from January 2008 to the current at Tianjin Eye Hospital and Beijing Children Hospital. All affected individuals underwent carefully ophthalmologic and orthoptic examinations, including best corrected visual acuities, the anterior segment and fundus, ocular alignment and ocular motility, binocular sensory status as well. Molecular diagnosis were performed for all affected individuals after informed consent. Mutations screening was performed by the Next-generation sequencing using a 7 gene panel including KIF21A , TUBB2, TUBB3,PHOX2A COL25A1,CHN1and ROBO3 genes associated with CCDDs.
Heterozygous KIF21A mutations were identified in 23 of 25 families with CFEOM, in which 21 of them carried c.2860C>T (p.R954W) mutation and two of them carried c.2861G>A(p.R954Q). Mutation of c.568C>T(p.R190C) in TUBB3 gene was detected in one family with CFEOM. A heterozygous ROBO 3 gene mutation of c.416G>T (p. Gly139Val) was identified in a patients with HGPPS who was misdiagnosed as untypical CFEOM before he developed progressive scolosis. However, no disease-causing gene mutations were detected in the patients with either DRS or MS. Patients with KIF21A mutation or TUBB3 gene mutation has the similar clinical characters of CFEOM showing bilateral blepharoptosis, chin elevation and infraduction of both eyes without ability to elevate either eye above the horizontal midline.
CCDDs has variable phenotype and expressivity depending on the types and amounts of the involved cranial nerves. Molecular consult is helpful for differentiate diagnosis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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