Delineation of EFTUD2 Haploinsufficiency‐Related Phenotypes Through a Series of 36 Patients |
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Authors: | Myriam Oufadem Géraldine Goudefroye Lucile Boutaud Jean‐Luc Alessandri Neus Baena Geneviève Baujat Clarisse Baumann Odile Boute‐Benejean Roseline Caumes Charles Decaestecker Dominique Gaillard Alice Goldenberg Marie Gonzales Muriel Holder‐Espinasse Marie‐Line Jacquemont Didier Lacombe Sylvie Manouvrier‐Hanu Sandrine Marlin Michèle Mathieu‐Dramard Gilles Morin Laurent Pasquier Florence Petit Marlène Rio Robert Smigiel Christel Thauvin‐Robinet Alexandre Vasiljevic Alain Verloes Valérie Malan Arnold Munnich Loïc de Pontual Michel Vekemans Stanislas Lyonnet Tania Attié‐Bitach Jeanne Amiel |
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Institution: | 1. Unité INSERM U1163, Faculté Paris‐Descartes, Institut IMAGINE, Paris, France;2. Département de Génétique, H?pital Necker‐Enfants Malades, APHP, Paris, France;3. P?le Enfants, H?pital Félix Guyon, CHRU de La Réunion, France;4. Centro Diagnóstico, Corporación Sanitaria Parc Taulí, Sabadell, Barcelone, Espagne;5. Département de génétique, H?pital Robert Debré, Paris, France;6. Service de Génétique Clinique, H?pital Jeanne de Flandre, CHRU Lille, France;7. Service de Génétique, H?pital Maison Blanche, CHRU Reims, France;8. Service de Génétique, H?pital Charles Nicolle, Rouen, France;9. Service de Génétique et embryologie médicales, H?pital d’Enfants Armand‐Trousseau, CHU Paris Est, France;10. Service de Génétique, CHU Bordeaux, Laboratoire MRGM, Université de Bordeaux, Bordeaux, France;11. Unité de Génétique clinique, H?pital Nord, CHU Amiens, France;12. Service de Génétique, CHU de Rennes, France;13. Katedra i Zaklad Genetyki Medycznej, Wroclaw, Pologne;14. Service de Génétique, H?pital d’Enfants, CHU de Dijon, France;15. Département de Pathologie et Neuropathologie, Groupement Hospitalier Est, Bron, France |
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Abstract: | Mandibulofacial dysostosis, Guion‐Almeida type (MFDGA) is a recently delineated multiple congenital anomalies/mental retardation syndrome characterized by the association of mandibulofacial dysostosis (MFD) with external ear malformations, hearing loss, cleft palate, choanal atresia, microcephaly, intellectual disability, oesophageal atresia (OA), congenital heart defects (CHDs), and radial ray defects. MFDGA emerges as a clinically recognizable entity, long underdiagnosed due to highly variable presentations. The main differential diagnoses are CHARGE and Feingold syndromes, oculoauriculovertebral spectrum, and other MFDs. EFTUD2, located on 17q21.31, encodes a component of the major spliceosome and is disease causing in MFDGA, due to heterozygous loss‐of‐function (LoF) mutations. Here, we describe a series of 36 cases of MFDGA, including 24 previously unreported cases, and we review the literature in order to delineate the clinical spectrum ascribed to EFTUD2 LoF. MFD, external ear anomalies, and intellectual deficiency occur at a higher frequency than microcephaly. We characterize the evolution of the facial gestalt at different ages and describe novel renal and cerebral malformations. The most frequent extracranial malformation in this series is OA, followed by CHDs and skeletal abnormalities. MFDGA is probably more frequent than other syndromic MFDs such as Nager or Miller syndromes. Although the wide spectrum of malformations complicates diagnosis, characteristic facial features provide a useful handle. |
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Keywords: | EFTUD2 spliceosome mandibulofacial dysostosis microcephaly |
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