Objective: To analyze the clinical characteristics of patients with Möbius syndrome (MBS) and to explore likely pathogenic genes. Methods: Cross-sectional study. The study enrolled 18 sporadic MBS patients who visited the Eye Center of Beijing Tongren Hospital Affiliated to Capital Medical University from July 2018 to December 2021. All patients completed the general information questionnaire and underwent detailed ophthalmic examinations and general physical examinations. Seventeen patients received MRI examination of cranial nerves and the orbit. The peripheral venous blood of all patients and their nuclear family members was collected, the genomic DNA was extracted, and the pathogenic gene variations that may lead to MBS were identified by whole exome sequencing and bioinformatics analysis. Results: Among the 18 patients, there were 8 males and 10 females, and the age was (4.5±4.0) years (range, 8 months to 17 years). All patients showed congenital, bilateral or unilateral abduction deficit and facial weakness, which met the minimum diagnostic criteria of MBS. Among them, bilateral abduction deficit (16/18) and bilateral facial weakness (15/18) were more common. Nine patients were orthotopic in primary position, eight presented with esotropia, and one showed hypotropia. All patients had ametropia, of which 4 patients were diagnosed as amblyopia. Fifteen patients were also accompanied by other multiple congenital malformations, mainly characterized by abnormal development of glossopharynx (14/18) and limbs (5/18), and 7 patients were also accompanied by motor retardation. In addition, 9 patients had intrauterine exposure to adverse factors. Among the 17 patients who underwent MRI, 15 patients had bilateral hypoplasia of the abducens nerve, two had unilateral hypoplasia of the abducens nerve, 14 showed bilateral hypoplasia of the facial nerve, and three showed hypoplasia of the left facial nerve. Besides, some patients were also accompanied by hypoplasia of other cranial nerves, mainly the glossopharyngeal nerve and the hypoglossal nerve. No definite pathogenic variations were found by whole exome sequencing and bioinformatics analysis. Conclusions: The main clinical features of MBS were congenital abduction deficit and facial weakness, with complicated manifestations and variable severity. MRI showed absence or thinning of the abducens nerve and the facial nerve. The results of MRI can be used as a supplement to the diagnostic criteria of MBS. The mutation detection rate of MBS was low, and half of patients had exposure to adverse factors during pregnancy, suggesting that there was a multifactorial pathogenic mechanism in MBS.
目的： 探讨临床罕见的Möbius综合征（MBS）的临床特征及可能的致病基因。 方法： 横断面研究。对2018年7月至2021年12月就诊于首都医科大学附属北京同仁医院北京同仁眼科中心的18例散发MBS患者进行一般信息问卷调查、详细眼科检查和全身体格检查，其中17例患者行颅神经及眼眶MRI。采集所有患者及核心家系成员的外周静脉血，提取基因组DNA，应用全外显子组测序及生物信息学分析方法鉴定可能导致MBS的致病基因变异。 结果： 在18例患者中，男性8例，女性10例；年龄为（4.5±4.0）岁（8个月至17岁）。18例患者均存在先天性单侧或双侧眼球外转受限及面瘫，符合MBS的最低诊断标准。其中，以双侧眼球外转受限（16例）及双侧面瘫（15例）更为多见。18例患者中，第一眼位正位9例，内斜视8例，下斜视1例。18例患者均患有屈光不正，其中4例诊断为弱视。15例患者伴多器官系统畸形，以舌咽（14例）和肢体发育异常（5例）为主，7例患者存在运动发育迟缓。9例患者存在孕期不良因素暴露。在17例行MRI检查的患者中，双侧展神经发育不良15例，单侧展神经发育不良2例；双侧面神经发育不良14例，左侧面神经发育不良3例；部分患者伴有其他颅神经发育不良，以舌咽神经、舌下神经为主。全外显子组测序及生物信息学分析未发现明确致病基因变异。 结论： MBS的核心临床特征为先天性眼球外转受限和面瘫，但临床表现多样且严重程度存在较大变异。所有行颅神经MRI检查的患者均存在展神经及面神经纤细或缺如，颅神经MRI检查结果可作为MBS诊断标准的补充。MBS的致病基因突变检出率较低，半数患者存在孕期不良因素暴露，提示MBS存在多因素致病机制。.