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Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients.
Hum Mutat. 2014 Apr; 35(4):478-85.HM

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.

Authors+Show Affiliations

Département de Génétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24470203

Citation

Lehalle, Daphné, et al. "Delineation of EFTUD2 Haploinsufficiency-related Phenotypes Through a Series of 36 Patients." Human Mutation, vol. 35, no. 4, 2014, pp. 478-85.
Lehalle D, Gordon CT, Oufadem M, et al. Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients. Hum Mutat. 2014;35(4):478-85.
Lehalle, D., Gordon, C. T., Oufadem, M., Goudefroye, G., Boutaud, L., Alessandri, J. L., Baena, N., Baujat, G., Baumann, C., Boute-Benejean, O., Caumes, R., Decaestecker, C., Gaillard, D., Goldenberg, A., Gonzales, M., Holder-Espinasse, M., Jacquemont, M. L., Lacombe, D., Manouvrier-Hanu, S., ... Amiel, J. (2014). Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients. Human Mutation, 35(4), 478-85. https://doi.org/10.1002/humu.22517
Lehalle D, et al. Delineation of EFTUD2 Haploinsufficiency-related Phenotypes Through a Series of 36 Patients. Hum Mutat. 2014;35(4):478-85. PubMed PMID: 24470203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients. AU - Lehalle,Daphné, AU - Gordon,Christopher T, AU - Oufadem,Myriam, AU - Goudefroye,Géraldine, AU - Boutaud,Lucile, AU - Alessandri,Jean-Luc, AU - Baena,Neus, AU - Baujat,Geneviève, AU - Baumann,Clarisse, AU - Boute-Benejean,Odile, AU - Caumes,Roseline, AU - Decaestecker,Charles, AU - Gaillard,Dominique, AU - Goldenberg,Alice, AU - Gonzales,Marie, AU - Holder-Espinasse,Muriel, AU - Jacquemont,Marie-Line, AU - Lacombe,Didier, AU - Manouvrier-Hanu,Sylvie, AU - Marlin,Sandrine, AU - Mathieu-Dramard,Michèle, AU - Morin,Gilles, AU - Pasquier,Laurent, AU - Petit,Florence, AU - Rio,Marlène, AU - Smigiel,Robert, AU - Thauvin-Robinet,Christel, AU - Vasiljevic,Alexandre, AU - Verloes,Alain, AU - Malan,Valérie, AU - Munnich,Arnold, AU - de Pontual,Loïc, AU - Vekemans,Michel, AU - Lyonnet,Stanislas, AU - Attié-Bitach,Tania, AU - Amiel,Jeanne, Y1 - 2014/03/05/ PY - 2013/11/06/received PY - 2014/01/10/accepted PY - 2014/1/29/entrez PY - 2014/1/29/pubmed PY - 2015/1/30/medline KW - EFTUD2 KW - mandibulofacial dysostosis KW - microcephaly KW - spliceosome SP - 478 EP - 85 JF - Human mutation JO - Hum Mutat VL - 35 IS - 4 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/24470203/Delineation_of_EFTUD2_haploinsufficiency_related_phenotypes_through_a_series_of_36_patients_ DB - PRIME DP - Unbound Medicine ER -