下颌面骨发育不全伴小头畸形(MFDM,OMIM#610536)是一种极其罕见的以小头畸形为特征的遗传综合征,外耳畸形,听力损失,和独特的面部外观,包括颧骨发育不全和小颌畸形。偶尔,其他内脏器官的各种畸形,包括食管闭锁或气管食管瘘,可能会导致危及生命的情况。EFTUD2的单倍不足是MFDM的原因。这里,我们介绍了6名通过分子遗传学检测诊断为MFDM的韩国儿童的表型和遗传特征.除一名患者外,所有患者的枕额周长均低于-2.0标准差评分。在所有患者中均发现了小颌畸形。腭裂(66.7%)和其他面部畸形,包括面部不对称(50%)和颌骨发育不全(50%),也经常被观察到。在所有患者中观察到听力损失以及一个或多个内耳和外耳畸形。包括听骨异常,耳道狭窄,和microtia。2例(33.3%)因气管食管瘘C型接受手术治疗。大多数患者最初被误诊为其他较知名的具有重叠特征的综合征,如叛徒柯林斯或CHARGE综合征。前三名患者使用外显子组测序进行诊断。然而,在前三名患者对MFDM的认识增加后,MFDM被认为是最初的鉴别诊断之一,可以通过其余3例的靶基因分析来诊断。因此,我们推荐有针对性的EFTUD2分析作为面部骨形成障碍患者MFDM快速诊断的初步检查,小头畸形,和耳科问题。
Mandibulofacial dysostosis with microcephaly (MFDM, OMIM#610536) is an extremely rare genetic syndrome characterised by microcephaly, external ear deformity, hearing loss, and distinct facial appearance, including zygomatic hypoplasia and micrognathia. Occasionally, various malformations in other internal organs, including oesophageal atresia or tracheoesophageal fistula, may lead to life-threatening situations. Haploinsufficiency of EFTUD2 is responsible for MFDM. Here, we present the phenotypic and genetic characteristics of six Korean children who were diagnosed with MFDM by molecular genetic testing. All but one patient had occipitofrontal circumferences below the -2.0 standard deviation score. Micrognathia was identified in all patients. A cleft palate (66.7%) and other facial dysmorphisms, including facial asymmetry (50%) and malar hypoplasia (50%), were also frequently observed. Hearing loss was observed in all patients along with one or more internal and external ear deformities, including ossicular anomalies, auditory canal stenosis, and microtia. Two patients (33.3%) had undergone surgery for tracheoesophageal fistula type C. Most patients were initially misdiagnosed as other better-known syndromes with overlapping characteristics, such as Treacher Collins or CHARGE syndrome. The first three patients were diagnosed using exome sequencing. However, after increased awareness of MFDM in the first three patients, MFDM was considered one of the initial differential diagnoses and could be diagnosed by target gene analysis in the remaining three cases. Thus, we recommend targeted EFTUD2 analysis as the initial workup for the rapid diagnosis of MFDM in patients with facial dysostosis, microcephaly, and otologic problems.