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Clinical and molecular delineation of mandibulofacial dysostosis with microcephaly in six Korean patients: When to consider EFTUD2 analysis?
Eur J Med Genet. 2022 May; 65(5):104478.EJ

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.

Authors+Show Affiliations

Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, South Korea.Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, South Korea.Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, South Korea. Electronic address: jmko@snu.ac.kr.Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, South Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35395430

Citation

Ryu, Jae Hui, et al. "Clinical and Molecular Delineation of Mandibulofacial Dysostosis With Microcephaly in Six Korean Patients: when to Consider EFTUD2 Analysis?" European Journal of Medical Genetics, vol. 65, no. 5, 2022, p. 104478.
Ryu JH, Kim HY, Ko JM, et al. Clinical and molecular delineation of mandibulofacial dysostosis with microcephaly in six Korean patients: When to consider EFTUD2 analysis? Eur J Med Genet. 2022;65(5):104478.
Ryu, J. H., Kim, H. Y., Ko, J. M., Kim, M. J., Seong, M. W., Choi, B. Y., & Chae, J. H. (2022). Clinical and molecular delineation of mandibulofacial dysostosis with microcephaly in six Korean patients: When to consider EFTUD2 analysis? European Journal of Medical Genetics, 65(5), 104478. https://doi.org/10.1016/j.ejmg.2022.104478
Ryu JH, et al. Clinical and Molecular Delineation of Mandibulofacial Dysostosis With Microcephaly in Six Korean Patients: when to Consider EFTUD2 Analysis. Eur J Med Genet. 2022;65(5):104478. PubMed PMID: 35395430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and molecular delineation of mandibulofacial dysostosis with microcephaly in six Korean patients: When to consider EFTUD2 analysis? AU - Ryu,Jae Hui, AU - Kim,Hwa Young, AU - Ko,Jung Min, AU - Kim,Man Jin, AU - Seong,Moon-Woo, AU - Choi,Byung Yoon, AU - Chae,Jong Hee, Y1 - 2022/04/05/ PY - 2021/08/08/received PY - 2022/03/05/revised PY - 2022/03/12/accepted PY - 2022/4/9/pubmed PY - 2022/4/20/medline PY - 2022/4/8/entrez KW - EFTUD2 KW - Guion-Almeida type KW - Mandibulofacial dysostosis KW - Mandibulofacial dysostosis with microcephaly KW - Spliceosomopathy KW - mandibulofacial dysostosis SP - 104478 EP - 104478 JF - European journal of medical genetics JO - Eur J Med Genet VL - 65 IS - 5 N2 - 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. SN - 1878-0849 UR - https://www.unboundmedicine.com/medline/citation/35395430/Clinical_and_molecular_delineation_of_mandibulofacial_dysostosis_with_microcephaly_in_six_Korean_patients:_When_to_consider_EFTUD2_analysis DB - PRIME DP - Unbound Medicine ER -