Prenatal Silver-Russell Syndrome in a Chinese Family Identified by Non-Invasive Prenatal Testing

Abstract

Russell-Silver syndrome (SRS) is a rare condition characterized by poor growth before and after birth along with multiple physical and psychosocial characteristics such as short stature, characteristic facial features, body asymmetry, feeding difficulties, and learning disabilities. In this study, we report a family with 2 recurrent SRS pregnancies due to a derivative chromosome 15 that is the result of a maternally derived t(11;15) translocation, detected by non-invasive prenatal testing (NIPT). The 2 SRS fetuses were diagnosed by chromosomal microarray analysis, but a balanced, reciprocal translocation of the mother was disclosed by the combination of routine karyotyping and FISH. This study demonstrates that NIPT has the ability to identify submicroscopic copy number variations (CNVs) in fetuses, which in some cases may result from a parent being a balanced rearrangement carrier. Because of the differences in resolution and the various benefits and limitations of each genetic technique, great care must be taken when deciding on which test(s) to employ in family studies.

Keywords: Chromosomal microarray; Non-invasive prenatal testing; Prenatal diagnosis; Silver-Russell syndrome.

Fig. 1

Analyses of chromosomal aberrations by non-invasive prenatal testing (NIPT), conventional cytogenetics, FISH, and microarray in the family with recurrent Silver-Russell syndrome. a NIPT result showing a 12.4-Mb gain on the short arm of chromosome 11. The blue line is the Stuffer Z-score. The purple line and black line are the corrected Z-score. Red asterisks represent the region of gain. Vertical axis: Z-score. Horizontal axis: chromosome localization. b Chromosome microarray analysis result showing array plot for the 11p15.5 region in the fetus. DNA copy number change is represented by the positive log2 ratio above the baseline. The CNV gain encompasses approximately 7.6 Mb, extending from 230,680 proximally to 7,894,535 distally. c Representative partial karyotypes of the mother and the fetus. The abnormal chromosomes are marked by arrows. d FISH analysis of metaphase chromosomes with 11pter (D11S2071) and 11qter (D11S4974) probes (LBP, Guangzhou, China) in the father and mother. Two probe signals specific for 11p15.5 were seen in the maternal metaphase chromosomes, with 1 signal localized on 15p. The arrows demonstrate the targeted der(15)t(11;15) and der(11)t(11;15) with probe signals.