Delineation of EFTUD2 Haploinsufficiency-Related Phenotypes Through a Series of 36 Patients

作者：Lehalle Daphne; Gordon Christopher T; Oufadem Myriam; Goudefroye Geraldine; Boutaud Lucile; Alessandri Jean Luc; Baena Neus; Baujat Genevieve; Baumann Clarisse; Boute Benejean Odile; Caumes Roseline; Decaestecker Charles; Gaillard Dominique; Goldenberg Alice; Gonzales Marie; Holder Espinasse Muriel; Jacquemont Marie Line; Lacombe Didier; Manouvrier Hanu Sylvie; Marlin Sandrine; Mathieu Dramard Michele; Morin Gilles; Pasquier Laurent; Petit Florence; Rio Marlene

来源：Human Mutation, 2014, 35(4): 478-485.

DOI：10.1002/humu.22517

• EFTUD2
• spliceosome
• mandibulofacial dysostosis
• microcephaly

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-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 EFTUD2LoF. 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.

• 出版日期2014-4