Congenital fibrosis of the extraocular muscles in a Czech family and its molecular genetic cause

Authors: Ľ. Ďuďáková 1;  E. Vyhnálková 2;  P. Sklenka 3;  P. Kuthan 3;  P. Diblík 3;  P. Lišková 1,3
Authors‘ workplace: Klinika dětského a dorostového lékařství, 1. LF UK a VFN v Praze 1;  Ústav biologie a lékařské genetiky, Oddělení klinické genetiky, FN Motol, Praha 2;  Oční klinika 1. LF UK a VFN v Praze 3
Published in: Cesk Slov Neurol N 2019; 82(5): 561-566
Category: Original Paper
doi: 10.14735/amcsnn2019561


Aim: Congenital fibrosis of the extraocular muscles (CFEOM) is a rare autosomal dominant disorder characterized by bilateral non-progressive ophthalmoplegia and ptosis. The aim of this study was to identify the molecular genetic cause in a four-generation family with CFEOM and to describe the clinical findings in four affected and one unaffected member.

Patients and methods: All patients underwent an eye examination. Exons 2, 8, 20 and 21 of the KIF21A gene were directly examined by Sanger sequencing in the proband. Sanger sequencing was also used to test for the presence of the detected mutation in other relatives.

Results: Clinical findings were typical in all affected individuals manifesting as ptosis and severely limited vertical and horizontal eye movements with compensatory backward tilt of the head. All patients also had decreased visual acuity attributed to amblyopia and synkinetic eye movements; synergistic convergence on attempted vertical gaze and divergence in the downgaze. A known heterozygous mutation c.2860C>T; p.(Arg954Trp) in KIF21A was identified in all available affected family members with CFEOM. This mutation was not found in a grandson of the proband who had no clinical disease symptoms.

Conclusion: CFEOM is a serious disorder leading to life-long functional and often psychological problems. The molecular genetic cause in patients of Czech origin has been discovered for the first time.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.




结果:在所有受影响的个体中,典型的临床表现为上睑下垂,垂直和水平眼运动严重受限以及头部向后倾斜。所有患者的视力均因弱视和眼球运动同步而下降;尝试垂直注视和向下注视的协同收敛。已知的杂合突变c.2860C> T;在所有可能患有CFEOM的受影响家庭成员中都发现了KIF21A中的p。(Arg954Trp)。在没有临床疾病症状的先证者的孙子中未发现此突变。


关键词:先天性眼外肌纤维化–下垂–眼肌麻痹– KIF21A


ptosis – ophthalmoplegia – KIF21A – congenital fibrosis of the extraocular muscles


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