Structural abnormalities of chromosome 8 and fetoplacental discrepancy: A second case report and review of fetal phenotype of 8p inverted duplication deletion syndrome

Abstract

We described a new second case of fetoplacental discrepancy involving first trimester prenatal detection of mosaic isochromosome i (8) (q10). A 32-year-old woman underwent chorionic villous sampling because of increased fetal nuchal translucency. Analysis of direct chromosome preparations was performed by R-banding and FISH using subtelomeric, centromeric and whole chromosome painting probes for chromosome 8 showing the presence of an isochromosome 8q with a complex, female mosaic karyotype: mos 46,XX,i (8) (q10)[13]/46,XX,del (8) (p23)[10]. Cytogenetic analysis of cultured CVS showed an interstitial duplication with concomitant terminal deletion of the short arm of chromosome 8: 46,XX,der (8)del (8) (p23)dup (8) (p?)[18]. Array-CGH analysis from cultured trophoblasts and fetal tissues revealed a 6.69 Mb terminal deletion in 8p23.3p23.1 associated with a 31.49 Mb duplication in 8p23.1p11.1. FISH analysis confirmed the 8p inverted duplication deletion syndrome. Moreover, polymorphic DNA marker analysis demonstrated that the derivative chromosome 8 was of maternal origin. FISH analysis of cultured peripheral blood lymphocytes showed that the mother also carried a cryptic paracentric inversion inv (8) (p23). Our report contributes to expand the fetal phenotype of 8p inverted duplication deletion syndrome and also provides further insight into the underlying mechanism of this rare genomic disorder.

Introduction

Chromosome 8p inverted duplication deletion syndrome (ORPHA: 96092) is a complex and uncommon chromosome disorder characterized by hypotonia, developmental delay, facial dysmorphism, central nervous abnormalities and congenital heart defects (Feldman et al., 1993). This syndrome has an estimated incidence of 1/10,000–30,000 liveborn infants. The most common terminal deletion breakpoint is located in the olfactory receptors gene clusters or defensin repeats (ORDRs) on 8p23.1 region. The invdupdel (8p) is composed of a distal deletion to 8p23.1 followed by an intermediate intact segment, and a proximal mirror duplication of various extensions (Garcia-Santiago et al., 2015). To date, only six prenatal cases of 8p inverted duplication deletion syndrome were recorded, of which two were diagnosed during the first trimester (Chen et al., 2016; MacMillin, 2000) (Table 1).

Constitutional isochromosome i (8) (q10) is rarely observed. To the best of our knowledge, only two cases have been reported. The typical prenatal example of fetoplacental discrepancy with the presence of mosaic isochromosome 8q was first described in 2003 by Soler et al. The fetus carries a mosaic, complex karyotype: mos 46,XX,i (8q)[7]/46,XX,del (8) (p11.2)[28] in CVS and 46,XX,dup (8) (p23p11.2) de novo in amniocytes. Moreover, a newborn male presenting type III truncus arteriosus and facial dysmorphism with isochromosome 8q has also been documented (Silengo et al., 2005).

Here, we report a new second prenatal case of fetoplacental discrepancy with the presence of mosaic isochromosome i (8) (q10)/terminal 8p deletion in direct CVS and invdupdel (8p) in the fetus with increased nuchal translucency, and review the prenatal features of previously reported invdupdel (8p) cases.