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Delineation of EFTUD 2 Haploinsufficiency‐Related Phenotypes Through a Series of 36 Patients
Author(s) -
Lehalle Daphné,
Gordon Christopher T.,
Oufadem Myriam,
Goudefroye Géraldine,
Boutaud Lucile,
Alessandri JeanLuc,
Baeeus,
Baujat Geneviève,
Baumann Clarisse,
BouteBenejean Odile,
Caumes Roseline,
Decaestecker Charles,
Gaillard Dominique,
Goldenberg Alice,
Gonzales Marie,
HolderEspinasse Muriel,
Jacquemont MarieLine,
Lacombe Didier,
ManouvrierHanu Sylvie,
Marlin Sandrine,
MathieuDramard Michèle,
Morin Gilles,
Pasquier Laurent,
Petit Florence,
Rio Marlène,
Smigiel Robert,
ThauvinRobinet Christel,
Vasiljevic Alexandre,
Verloes Alain,
Malan Valérie,
Munnich Arnold,
Pontual Loïc,
Vekemans Michel,
Lyonnet Stanislas,
AttiéBitach Tania,
Amiel Jeanne
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22517
Subject(s) - microcephaly , haploinsufficiency , choanal atresia , biology , atresia , intellectual disability , charge syndrome , ciliopathies , genetics , dermatology , phenotype , anatomy , medicine , gene
Mandibulofacial dysostosis, G uion‐ A lmeida 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 ( CHD s), 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 F eingold syndromes, oculoauriculovertebral spectrum, and other MFD s. EFTUD 2 , located on 17q21.31, encodes a component of the major spliceosome and is disease causing in MFDGA , due to heterozygous loss‐of‐function ( L o F ) 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 EFTUD 2 L o F . 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 CHD s and skeletal abnormalities. MFDGA is probably more frequent than other syndromic MFD s such as N ager or M iller syndromes. Although the wide spectrum of malformations complicates diagnosis, characteristic facial features provide a useful handle.