title: Esophageal atresia, hypoplasia of zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and mental retardation--new MCA/MR syndrome in two affected sibs and a mildly affected mother?
abstract: The previously undescribed combination of esophageal atresia, hypoplasia of the zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and mental retardation was diagnosed in two siblings of different sexes, with the brother being more severely affected. The mother presented with zygomatic arch hypoplasia of the right side only. We discuss major differential diagnoses: Goldenhar, Feingold, CHARGE, and Treacher Collins syndromes show a few overlapping clinical features, but these diagnoses are unlikely as the clinical findings are unusual for Goldenhar syndrome and mutational screening of the MYCN, the CHD7, and the TCOF1 genes did not reveal any abnormalities. Autosomal recessive oto-facial syndrome, hypomandibular faciocranial dysostosis, and Ozkan syndromes were clinically excluded. A microdeletion 22q11.2 was excluded by FISH analysis, a microdeletion 2p23-p24 by microsatellite analyses, a subtelomeric chromosomal aberration by MLPA, and a small genomic deletion/duplication by CGH array. As X-inactivation studies did not show skewed X-inactivation in the mother, we consider X-chromosomal recessive inheritance of this condition less likely. We discuss autosomal dominant inheritance with variable expressivity or mosaicism in the mother as the likely genetic mechanism in this new multiple congenital anomaly/mental retardation (MCA/MR) syndrome.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Germany, and Department of Medical Genetics, Addenbrooke's Hospital, Cambridge, UK. dagmar.wieczorek@uni-due.de
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Charles
authors.initials: C
authors.lastname: Shaw-Smith
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmitt
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.forename: Alison
authors.initials: A
authors.lastname: Coffey
authors.forename: Eleanor
authors.initials: E
authors.lastname: Howard
authors.forename: Ute
authors.initials: U
authors.lastname: Hehr
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
mesh_terms: D000015:Abnormalities, Multiple; D002648:Child; D004431:Ear, External / Q000002:abnormalities*; D004933:Esophageal Atresia / Q000150:complications*; D005260:Female; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging; D006330:Heart Defects, Congenital / Q000150:complications*; D006801:Humans; D008607:Intellectual Disability / Q000150:complications*; D008297:Male; D008831:Microcephaly / Q000150:complications*; D009035:Mothers; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D035781:Siblings; D012886:Skull / Q000000981:diagnostic imaging; D013131:Spine / Q000000981:diagnostic imaging; D013577:Syndrome; D015050:Zygoma / Q000002:abnormalities*