ABSTRACT
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.