Christina Kehrer1, Alexander Hoischen2, Ralf Menkhaus3, Eva Schwab4, Andreas Müller5, Sarah Kim6, Martina Kreiß6, Valerie Weitensteiner6, Alina Hilger6, Christoph Berg1, Anne Geipel1, Heiko Reutter5,6, Ulrich Gembruch7. 1. Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany. 2. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. 3. Center for Assisted Reproduction and Prenatal Diagnosis, Minden, Germany. 4. Medical Office for Human Genetics, Wiesbaden, Germany. 5. Department of Neonatology and Pediatric Intensive Care, University of Bonn, Bonn, Germany. 6. Institute of Human Genetics, University of Bonn, Bonn, Germany. 7. Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany. ulrich.gembruch@ukb.uni-bonn.de.
Abstract
OBJECTIVE: Simpson-Golabi-Behmel (SGBS) syndrome type 1 and type 2 represent rare X-linked prenatal overgrowth disorders. The aim of our study is to describe the prenatal sonographic features as well as the genetic work-up. METHOD: Retrospective analysis of four cases with a pre- or postnatal diagnosis of SGBS in a single tertiary referral center within a period of 4 years. RESULTS: In the study period, four male fetuses with SGBS were detected. The final diagnosis was made prenatally in three cases. In all cases the second trimester anomaly scan revealed left sided congenital diaphragmatic hernia (CDH) with additional anomalies; three fetuses with SGBS type 1 showed fetal overgrowth. In two of these, whole exome sequencing showed a possible frameshift mutation and a point mutation in the gene GPC3, respectively. In the third case, multiplex ligation-dependent probe amplification (MLPA) revealed a hemizygous duplication of exon 3-7 in the gene GPC3. In the fourth case, SGBS type 2 was confirmed by array comparative genomic hybridization (CGH) of amniotic fluid cells showing a deletion of the gene OFD1. CONCLUSION: We could demonstrate, that in the presence of a CDH, syndromes of the fetus can be increasingly differentiated by detailed sonography followed by a selective and graded molecular diagnostic using microarray techniques and whole exome sequencing.
OBJECTIVE:Simpson-Golabi-Behmel (SGBS) syndrome type 1 and type 2 represent rare X-linked prenatal overgrowth disorders. The aim of our study is to describe the prenatal sonographic features as well as the genetic work-up. METHOD: Retrospective analysis of four cases with a pre- or postnatal diagnosis of SGBS in a single tertiary referral center within a period of 4 years. RESULTS: In the study period, four male fetuses with SGBS were detected. The final diagnosis was made prenatally in three cases. In all cases the second trimester anomaly scan revealed left sided congenital diaphragmatic hernia (CDH) with additional anomalies; three fetuses with SGBS type 1 showed fetal overgrowth. In two of these, whole exome sequencing showed a possible frameshift mutation and a point mutation in the gene GPC3, respectively. In the third case, multiplex ligation-dependent probe amplification (MLPA) revealed a hemizygous duplication of exon 3-7 in the gene GPC3. In the fourth case, SGBS type 2 was confirmed by array comparative genomic hybridization (CGH) of amniotic fluid cells showing a deletion of the gene OFD1. CONCLUSION: We could demonstrate, that in the presence of a CDH, syndromes of the fetus can be increasingly differentiated by detailed sonography followed by a selective and graded molecular diagnostic using microarray techniques and whole exome sequencing.
Authors: Jingjing Xiang; Qin Zhang; Xiaoyan Song; Yinghua Liu; Haibo Li; Hong Li; Ting Wang Journal: J Int Med Res Date: 2019-07-15 Impact factor: 1.671
Authors: Nunziana Pezzella; Guglielmo Bove; Roberta Tammaro; Brunella Franco Journal: Am J Med Genet C Semin Med Genet Date: 2022-02-02 Impact factor: 3.359