Whole exome sequencing and array‐based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson–Golabi–Behmel syndrome. (27th September 2016)

• Record Type: Journal Article
• Authors: Kehrer, Christina; Hoischen, Alexander; Menkhaus, Ralf; Schwab, Eva; Müller, Andreas; Kim, Sarah; Kreiß, Martina; Weitensteiner, Valerie; Hilger, Alina; Berg, Christoph; Geipel, Anne; Reutter, Heiko; Gembruch, Ulrich
• Is Part Of: Prenatal diagnosis. Volume 36:Number 10(2016)
• Page Start: 961
• Page End: 965
• Publication Date: 2016-09-27
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4920
• Languages: English
• ISSNs: 0197-3851

Abstract

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. © 2016 John Wiley & Sons, Ltd. Abstract : What's Already Known About This Topic? Simpson–Golabi–Behmel syndrome (SGBS) type 1 and type 2 are rare overgrowth syndromes. Diagnosis can be suggested in the second trimester by prenatal ultrasound based on fetal overgrowth and associated congenital anomalies, but prenatal diagnosis remains elusive in many cases. What Does This Study Add? Here we show how modern molecular genetics using whole exome sequencing or microarrays can aid the prenatal diagnosis of fetuses suspected to have SGBS.