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Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients.
Am J Med Genet A. 2017 Dec; 173(12):3136-3142.AJ

Abstract

Frontonasal dysplasias are rare congenital malformations of frontonasal process-derived structures, characterized by median cleft, nasal anomalies, widely spaced eyes, and cranium bifidum occultum. Several entities of syndromic frontonasal dysplasia have been described, among which, to date, only a few have identified molecular bases. We clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. We identified six individuals with a similar phenotype, including one discordant monozygous twin. Facial features were remarkable by nasal deformity with creased ridge and depressed or absent tip, widely spaced eyes, almond-shaped palpebral fissures, and downturned corners of the mouth. All had apparently normal psychomotor development. In addition, upper limb anomalies, frontonasal encephalocele, corpus callosum agenesis, choanal atresia, and congenital heart defect were observed. We identified five reports in the literature of patients presenting with the same phenotype. Exome sequencing was performed on DNA extracted from blood of two individuals, no candidate gene was identified. In conclusion, we report six novel simplex individuals presenting with a specific frontonasal dysplasia entity associating recognizable facial features, limb and visceral malformations, and apparently normal development. The identification of discordant monozygotic twins supports the hypothesis of a mosaic disorder. Although previous patients have been reported, this is the first series, allowing delineation of a clinical subtype of frontonasal dysplasia, paving the way toward the identification of its molecular etiology.

Authors+Show Affiliations

Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Centre Hospitalier Universitaire Dijon, Dijon, France.Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France.Service de Neurochirurgie, Hôpital Necker, Paris, France.Genetic Departement for Rare Disease and Personalised Medicine, Clinical Division, CHU Montpellier, Montpellier, France.Department of Plastic & Reconstructive Surgery, College of Medicine, University of Ulsan, Seoul Asan Medical Center, Seoul, South Korea.Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.Pediatric Genetics, Pediatric Hematology Oncology Research & Training Hospital, Ankara, Turkey.Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.Genetic Departement for Rare Disease and Personalised Medicine, Clinical Division, CHU Montpellier, Montpellier, France.Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Centre Hospitalier Universitaire Dijon, Dijon, France.Pediatrics and Medical Genetics, Barzilai Medical Center, Ashkelon, Israel.Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Centre Hospitalier Universitaire Dijon, Dijon, France.Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France.Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. Department of Medical Genetics, Koç University School of Medicine (KUSoM), Zeytinburnu, İstanbul, Turkey.Equipe GAD, INSERM LNC UMR 1231, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Centre Hospitalier Universitaire Dijon, Dijon, France.

Pub Type(s)

Case Reports
Journal Article
Review

Language

eng

PubMed ID

29136349

Citation

Lehalle, Daphné, et al. "Clinical Delineation of a Subtype of Frontonasal Dysplasia With Creased Nasal Ridge and Upper Limb Anomalies: Report of Six Unrelated Patients." American Journal of Medical Genetics. Part A, vol. 173, no. 12, 2017, pp. 3136-3142.
Lehalle D, Altunoglu U, Bruel AL, et al. Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients. Am J Med Genet A. 2017;173(12):3136-3142.
Lehalle, D., Altunoglu, U., Bruel, A. L., Arnaud, E., Blanchet, P., Choi, J. W., Désir, J., Kiliç, E., Lederer, D., Pinson, L., Thauvin-Robinet, C., Singer, A., Thevenon, J., Callier, P., Kayserili, H., & Faivre, L. (2017). Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients. American Journal of Medical Genetics. Part A, 173(12), 3136-3142. https://doi.org/10.1002/ajmg.a.38490
Lehalle D, et al. Clinical Delineation of a Subtype of Frontonasal Dysplasia With Creased Nasal Ridge and Upper Limb Anomalies: Report of Six Unrelated Patients. Am J Med Genet A. 2017;173(12):3136-3142. PubMed PMID: 29136349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients. AU - Lehalle,Daphné, AU - Altunoglu,Umut, AU - Bruel,Ange-Line, AU - Arnaud,Eric, AU - Blanchet,Patricia, AU - Choi,Jong-Woo, AU - Désir,Julie, AU - Kiliç,Esra, AU - Lederer,Damien, AU - Pinson,Lucile, AU - Thauvin-Robinet,Christel, AU - Singer,Amihood, AU - Thevenon,Julien, AU - Callier,Patrick, AU - Kayserili,Hulya, AU - Faivre,Laurence, PY - 2017/05/18/received PY - 2017/08/11/revised PY - 2017/08/21/accepted PY - 2017/11/15/entrez PY - 2017/11/15/pubmed PY - 2018/3/22/medline KW - frontonasal dysplasia KW - nasal malformation KW - nasofrontal encephalocele SP - 3136 EP - 3142 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 173 IS - 12 N2 - Frontonasal dysplasias are rare congenital malformations of frontonasal process-derived structures, characterized by median cleft, nasal anomalies, widely spaced eyes, and cranium bifidum occultum. Several entities of syndromic frontonasal dysplasia have been described, among which, to date, only a few have identified molecular bases. We clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. We identified six individuals with a similar phenotype, including one discordant monozygous twin. Facial features were remarkable by nasal deformity with creased ridge and depressed or absent tip, widely spaced eyes, almond-shaped palpebral fissures, and downturned corners of the mouth. All had apparently normal psychomotor development. In addition, upper limb anomalies, frontonasal encephalocele, corpus callosum agenesis, choanal atresia, and congenital heart defect were observed. We identified five reports in the literature of patients presenting with the same phenotype. Exome sequencing was performed on DNA extracted from blood of two individuals, no candidate gene was identified. In conclusion, we report six novel simplex individuals presenting with a specific frontonasal dysplasia entity associating recognizable facial features, limb and visceral malformations, and apparently normal development. The identification of discordant monozygotic twins supports the hypothesis of a mosaic disorder. Although previous patients have been reported, this is the first series, allowing delineation of a clinical subtype of frontonasal dysplasia, paving the way toward the identification of its molecular etiology. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/29136349/Clinical_delineation_of_a_subtype_of_frontonasal_dysplasia_with_creased_nasal_ridge_and_upper_limb_anomalies:_Report_of_six_unrelated_patients_ L2 - https://doi.org/10.1002/ajmg.a.38490 DB - PRIME DP - Unbound Medicine ER -