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Fetal Presentation of MYRF-Related Cardiac Urogenital Syndrome: An Emerging and Challenging Prenatal Diagnosis

Title: Fetal Presentation of MYRF-Related Cardiac Urogenital Syndrome: An Emerging and Challenging Prenatal Diagnosis
Authors: Favier, Maud; Brischoux-Boucher, Elise; Pyle, Louise C.; Mottet, Nicolas; Auber-Lenoir, Marion; Cattin, Julie; Dahlen, Sven-Eric; Cabrol, Christelle; Arbez-Gindre, Francine; Attie-Bitach, Tania; Boute, Odile; Devisme, Louise; Trost, Detlef; Boughalem, Aicha; Chitayat, David; Prasov, Lev; Chorin, Odelia; Rein-Rothschild, Annick; Kassif, Eran; Weissbach, Tal; Hendon, Laura Godfrey; Adam, Margaret P.; Quélin, Chloé; Jaillard, Sylvie; Mary, Laura; Aukema, Sietse M.; Heijligers, Malou; de Die-Smulders, Christine; Stegmann, Sander; Badalato, Lauren; Ben-Yehuda, Adi; Beneteau, Claire; Forey, Pierre-Louis; Kuentz, Paul; Piard, Juliette
Contributors: Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon); Centre de génétique humaine CHRU Besançon; Société Française de Foetopathologie Paris (SOFFOET); Children’s Hospital of Philadelphia (CHOP); Université de Bourgogne (UB); Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute) (institut GIMI); Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc Dijon (UNICANCER/CRLCC-CGFL); UNICANCER-UNICANCER-Établissement Français du Sang Bourgogne-Franche-Comté Besançon (EFS BFC - Besançon); Établissement Français du Sang La Plaine Saint-Denis (EFS)-Établissement Français du Sang La Plaine Saint-Denis (EFS)-FHU TRANSLAD (CHU de Dijon); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Laboratoire de Biologie Médicale SeqOIA Paris (seqOIA); Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Laboratoire CERBA Saint Ouen l'Aumône; Mount Sinai Hospital Toronto, Canada (MSH); University of Toronto; Université du Michigan = University of Michigan Ann Arbor (UMich); The Edmond and Lily Safra Center for brain sciences Jérusalem (ELSC); The Hebrew University of Jerusalem (HUJ); Chaim Sheba Medical Center; Tel Aviv University (TAU); University of Mississippi Medical Center (UMMC); Seattle Children’s Hospital; Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Université de Rennes (UR); Carl Von Ossietzky Universität Oldenburg = Carl von Ossietzky University of Oldenburg (OFFIS); Maastricht University Medical Centre (MUMC); Maastricht University Maastricht; Queen's University Kingston, Canada; Shaare Zedek Medical Center Jerusalem, Israel; Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux); Université de Bordeaux (UB); CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA); Université Grenoble Alpes (UGA); Lipides - Nutrition - Cancer Dijon - U1231 (LNC); Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro); National Eye Institute K08EY032098
Source: ISSN: 0197-3851.
Publisher Information: CCSD; Wiley
Publication Year: 2024
Subject Terms: [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Description: International audience ; Purpose: MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant.Methods: Detailed radiographic, pathological, clinical, and molecular data from 12 prenatal cases were collected through an international collaborative study. Adding the five fetuses previously published, we were able to study a cohort of 17 cases.Results: Main ultrasound-accessible manifestations of MYRF-CUGS include congenital heart defects (13/17, 76%), congenital diaphragmatic hernia (10/17, 59%) and disorders of sexual differentiation in 46, XY fetuses (7/14; 50%). Postnatal examination and/or autopsy data highlighted additional birth defects and neurological findings with a large spectrum of severity. Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants).Conclusion: We report the first prenatal cohort of MYRF-CUGS, allowing us to further characterize the variable expressivity of this rare disorder in fetuses. Severe congenital anomalies with a poor prognosis are more frequent than previously described in postnatal cases. Our data suggest that MYRF-CUGS is characterized by a recurrent recognizable malformative association, accessible to prenatal diagnosis, with a significant intrafamilial phenotypic variability making genetic counseling challenging.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/39542847; PUBMED: 39542847; PUBMEDCENTRAL: PMC11628210
DOI: 10.1002/pd.6700
Availability: https://hal.science/hal-04836387; https://hal.science/hal-04836387v1/document; https://hal.science/hal-04836387v1/file/Prenatal%20Diagnosis%20-%202024%20-%20Favier%20-%20Fetal%20Presentation%20of%20MYRF%E2%80%90Related%20Cardiac%20Urogenital%20Syndrome%20An%20Emerging%20and.pdf; https://doi.org/10.1002/pd.6700
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.12BD5310
Database: BASE