Objective:To explore the clinical diagnosis, otological treatment and molecular etiology in a rare syndromic hearing loss case characterized by mandibulofacial dysostosis with microcephaly（MFDM）. Methods: The proband underwent detailed history collection, systematic physical examination and phenotypic analysis, as well as audiological examination, chest X-ray, temporal bone CT and brain MRI and other imaging examinations. The blood DNA of the proband and his parents was extracted and tested by the whole exom sequencing. The EFTUD2-related-MFDM literatures published by the end of 2020 were searched and sifted in PubMed and CNKI databases,the clinical characteristics of MFDM were summarized. Results:In this study, the patient presented with hypoplasia of auricle, micrognathia, microcephaly, developmental retardation, severe sensorineural hearing loss in both ears, and developmental malformation of middle and inner ear. Genetic analysis revealed a de novo deletion c.623_624delAT in EFTUD2 gene. According to the clinical features and genetic test results, the patient was diagnosed as MFDM. In order to solve the problem of hearing loss, the patient was further performed bilateral cochlear implantation, and part of the electrodes responded well during and after operation. Conclusion:This is the first domestic reported case of MFDM caused by EFTUD2 gene mutation. The key problem of cochlear implantation for this kind of patient is to avoid damaging the malformed facial nerve during the operation.The effect of speech rehabilitation after cochlear implant operation is related to many factors such as intelligence development of the patients.
目的：分析探讨罕见的下颌骨颜面发育不全伴小头畸形（MFDM）的临床诊断、耳科学治疗以及分子病因学特征。 方法：对先证者进行详细的病史采集，系统查体及表型特征分析，以及听力学检查，胸部X线、颞骨CT和颅脑MRI等影像学检查。同时提取先证者及其父母血液DNA进行全外显子组测序，并检索PubMed、中国知网数据库，对截止2020年底前报道的由EFTUD2基因突变导致的MFDM临床特征进行筛选、归纳和总结。 结果：患儿表现为耳廓发育不良、小下颌、小头畸形，同时合并发育迟缓、双耳极重度感音神经性聋，中耳及内耳发育畸形，基因学检测发现EFTUD2基因的新生缺失变异c.623_624delAT。根据临床特征及基因学检测结果诊断为MFDM。行双侧人工耳蜗植入手术，术中及开机后部分电极反应良好。 结论：这是国内首次报道的EFTUD2基因突变导致的MFDM，对该患儿进行人工耳蜗植入术的关键在于术中避免损伤畸形的面神经，术后言语康复效果与患儿智力发育等多因素相关。.

The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.