To compare the clinical and neuroimaging phenotypes in Chinese patients with congenital fibrosis of extraocular muscles (CFEOM) harboring KIF21A versus TUBB3 variants. Retrospective, observational case series. A retrospective review of 37 CFEOM patients harboring mutations of KIF21A (n = 25) and TUBB3 (n = 12) with clinical examinations was performed. MRI was used to evaluate orbital, encephalic, and intracranial nerve integrity. The diameters of oculomotor nerve (CN3) and abducens nerves (CN6), the cross-section area (CSA) of the optic nerve (ON) and the volumes of extraocular muscles (EOMs) were measured in the mutant groups and normal control group (n = 20). The CFEOM-KIF21A group had a slightly higher percentage of bilateral blepharoptosis (95% vs. 70%) and synergistic convergence (40% vs. 20%) compared with the CFEOM-TUBB3 group. The diameter of CN3 and the CSA of ON were significantly smaller in the mutant groups than the control. The median diameter of CN6 was smaller in the KIF21A group than in the TUBB3 group (P < 0.001). The median volumes of the superior rectus, lateral rectus, and inferior oblique muscle in the KIF21A group were significantly smaller than TUBB3 group. 10% of KIF21A families and 40% of TUBB3 families were accompanied by systemic congenital malformation (P = 0.070). Most of the CFEOM-KIF21A patients occur as isolated cases, tend to suffer a more severe ocular phenotype and CN6 hypoplasia. CFEOM-TUBB3 patients tend to present with syndromic CFEOM, systemic involvement is mainly associated with brain malformations, and appear to have a clear genotype-phenotype correlation.

Congenital fibrosis of extraocular muscles (CFEOM) syndrome is a genetically determined congenital disorder characterized by non-progressive ophthalmoplegia, restrictive ocular fixation, and ptosis. Its estimated incidence is approximately 1 in 230 000 to 250 000. This paper reports a family with type 3 CFEOM diagnosed at the Second Xiangya Hospital of Central South University. The proband was a 10-year-old female who presented with right esotropia and right upper eyelid ptosis. Whole-exome sequencing revealed a heterozygous c.904G>A mutation in the TUBB3 gene. Genetic testing of family members identified that the proband's mother carried the same mutation and exhibited left eyelid ptosis. The child underwent strabismus correction followed by ptosis repair, both of which led to marked postoperative improvement. For children presenting with congenital extraocular movement restriction and ptosis, genetic testing plays a crucial role in confirming the diagnosis and guiding family analysis. Additionally, individualized surgical intervention can significantly improve both ocular function and cosmetic appearance. 先天性眼外肌纤维化(congenital fibrosis of extraocular muscles，CFEOM)综合征是一种具有遗传倾向的先天性眼外肌功能障碍性疾病，患者典型表现为先天性非进展性眼外肌麻痹、限制性眼球固定及上睑下垂，发病率为1/23万~1/25万。本文报告中南大学湘雅二医院收治的1个CFEOM 3型家系，先证者为10岁女性患儿，临床表现为右眼向内偏斜合并右眼上睑下垂。全外显子组测序发现患者在TUBB3基因上发生c.904G>A杂合突变。对家系中其他成员检测的结果提示患者母亲也携带相同突变，表现为左眼眼睑下垂。先后予患儿斜视矫正手术、上睑下垂矫正手术，术后症状得到明显改善。对于出现先天性眼外肌运动障碍及上睑下垂的患者，应高度重视遗传学检测在确诊及家系分析中的价值;同时，个体化的手术干预可显著改善患者的功能及外观。.

Background Congenital fibrosis of the extraocular muscles (CFEOM) is a non-progressive sporadic or familial disease characterized by abnormal innervation of the extraocular muscles. This study aims to evaluate the types of diseases, management steps, and surgical outcomes. Methodology A total of 76 patients diagnosed with CFEOM between 2000 and 2022 were evaluated retrospectively. Patients were divided into CFEOM 1, 2, or 3 based on clinical findings. Preoperative and postoperative ocular deviations, as well as abnormal head positions (AHPs), of the patients were evaluated. Excellent outcomes for the head position were defined as less than 5°, good as less than 10°, and poor as greater than 10°. Excellent alignment for strabismus was considered to be less than 10 prism diopters (PD), good as less than 20 PD, and poor as greater than 20 PD. Results The average age at the first surgery in our clinic was 11.6 (1-51) years. The mean follow-up was 28.6 ± 7.4 months (range = 4-56 months). Type 1 disease was detected in 48 (63.2%) patients, type 2 disease in eight (10.5%), and type 3 disease in 20 (26.3%) patients. Of the 49 patients with AHP, 20 achieved excellent outcomes, 17 had good outcomes, and the remaining had poor outcomes. Ocular alignment in the primary position following the latest surgery was excellent in 30 patients, good in 26 patients, and poor in 20 patients. Conclusions No single best surgical method can be universally applied to every patient diagnosed with CFEOM. Patients must be evaluated individually and carefully, and the appropriate surgical procedure must be chosen. In this way, satisfactory gaze alignment and improvement of the AHP can be achieved.

Here, we have reported the genetic and clinical characteristics of four generations of a family patient from China with congenital fibrosis of extraocular muscles 1 (CFEOM1) and keratoconus (KC). The history of diseases, clinical observations, and blood samples of all family members were collected. A total of 100 healthy participants were recruited as normal controls. The whole exome sequencing of the genomic DNA and polymerase chain reaction were performed on samples obtained from the controls and their family members to verify the gene variants. The functional analyses of the variants were performed by using different software. Two single nucleotide polymorphisms were detected in the proband and other patients in his families, including a heterozygous missense variation, g.39726207C > T (c.2860C > T, p.R954W, rs121912585), in the third highly conserved coiled-coil domain of KIF21A, and a heterozygous missense variant, g.30664732A > C (c.136A > C, p.S46R, rs200111443) in TGFBR2. The variant p.R954W in KIF21A was predicted to be pathogenic using software, whereas p.S46R in TGFBR2 was predicted to be of uncertain significance (VUS). Thus, KC might have occurred in the proband and his daughter because of a combination of genetic mutations and involuntary eye rubbing induced by CFEOM1. This is the first case of concomitant KC in a family having CFEOM1. Thus, the study provides new information about patients with KC having CFEOM1. Furthermore, the study suggests that attention should be paid to the early detection and diagnosis of KC in patients with CFEOM1.