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Mandibulofacial dysostosis with microcephaly: An expansion of the phenotype via parental survey.
Am J Med Genet A. 2021 02; 185(2):413-423.AJ

Abstract

Mandibulofacial dysostosis with microcephaly (MFDM) is due to haploinsufficiency of spliceosomal GTPase EFTUD2. Features include microcephaly, craniofacial dysmorphology, developmental disability, and other anomalies. We surveyed parents of individuals with MFDM to expand knowledge about health, development, and parental concerns. Participants included attendees of the inaugural MFDM family conference in June 2019 and members of the MFDM online group. To explore MFDM variable expressivity, we offered targeted Sanger sequencing for untested parents. Forty-seven parents participated in the survey. 59% of individuals with MFDM were male, with mean age 6.4 years (range 8 months to 49 years). Similar to the literature (n = 123), common features include microcephaly, cleft palate, choanal stenosis, tracheoesophageal fistula, heart problems, and seizures. New information includes airway intervention details, age-based developmental outcomes, rate of vision refractive errors, and lower incidences of prematurity and IUGR. Family concerns focused on development, communication, and increased support. Targeted Sanger sequencing for families of seven individuals demonstrated de novo variants, for a total of 91.9% de novo EFTUD2 variants (n = 34/37). This study reports the largest single cohort of individuals with MFDM, expands phenotypic spectrum and inheritance patterns, improves understanding of developmental outcomes and care needs, and identifies development as the biggest concern for parents.

Authors+Show Affiliations

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Division of Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Department of Pediatrics, University of Missouri - Kansas City, Kansas City, Missouri, USA. Division of Clinical Genetics, Children's Mercy Kansas City, Kansas City, Missouri, USA.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

33247512

Citation

Abell, Katherine, et al. "Mandibulofacial Dysostosis With Microcephaly: an Expansion of the Phenotype Via Parental Survey." American Journal of Medical Genetics. Part A, vol. 185, no. 2, 2021, pp. 413-423.
Abell K, Hopkin RJ, Bender PL, et al. Mandibulofacial dysostosis with microcephaly: An expansion of the phenotype via parental survey. Am J Med Genet A. 2021;185(2):413-423.
Abell, K., Hopkin, R. J., Bender, P. L., Jackson, F., Smallwood, K., Sullivan, B., Stottmann, R. W., Saal, H. M., & Weaver, K. N. (2021). Mandibulofacial dysostosis with microcephaly: An expansion of the phenotype via parental survey. American Journal of Medical Genetics. Part A, 185(2), 413-423. https://doi.org/10.1002/ajmg.a.61977
Abell K, et al. Mandibulofacial Dysostosis With Microcephaly: an Expansion of the Phenotype Via Parental Survey. Am J Med Genet A. 2021;185(2):413-423. PubMed PMID: 33247512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mandibulofacial dysostosis with microcephaly: An expansion of the phenotype via parental survey. AU - Abell,Katherine, AU - Hopkin,Robert J, AU - Bender,Patricia L, AU - Jackson,Farrah, AU - Smallwood,Kelly, AU - Sullivan,Bonnie, AU - Stottmann,Rolf W, AU - Saal,Howard M, AU - Weaver,K Nicole, Y1 - 2020/11/27/ PY - 2020/06/12/received PY - 2020/10/09/revised PY - 2020/10/30/accepted PY - 2020/11/29/pubmed PY - 2021/7/8/medline PY - 2020/11/28/entrez KW - EFTUD2 KW - MFDM KW - acrofacial dysostosis KW - mandibulofacial dysostosis KW - mandibulofacial dysostosis with microcephaly KW - needs assessment SP - 413 EP - 423 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 185 IS - 2 N2 - Mandibulofacial dysostosis with microcephaly (MFDM) is due to haploinsufficiency of spliceosomal GTPase EFTUD2. Features include microcephaly, craniofacial dysmorphology, developmental disability, and other anomalies. We surveyed parents of individuals with MFDM to expand knowledge about health, development, and parental concerns. Participants included attendees of the inaugural MFDM family conference in June 2019 and members of the MFDM online group. To explore MFDM variable expressivity, we offered targeted Sanger sequencing for untested parents. Forty-seven parents participated in the survey. 59% of individuals with MFDM were male, with mean age 6.4 years (range 8 months to 49 years). Similar to the literature (n = 123), common features include microcephaly, cleft palate, choanal stenosis, tracheoesophageal fistula, heart problems, and seizures. New information includes airway intervention details, age-based developmental outcomes, rate of vision refractive errors, and lower incidences of prematurity and IUGR. Family concerns focused on development, communication, and increased support. Targeted Sanger sequencing for families of seven individuals demonstrated de novo variants, for a total of 91.9% de novo EFTUD2 variants (n = 34/37). This study reports the largest single cohort of individuals with MFDM, expands phenotypic spectrum and inheritance patterns, improves understanding of developmental outcomes and care needs, and identifies development as the biggest concern for parents. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/33247512/Mandibulofacial_dysostosis_with_microcephaly:_An_expansion_of_the_phenotype_via_parental_survey_ DB - PRIME DP - Unbound Medicine ER -