True trisomy 2 mosaicism in amniocytes and newborn liver associated with multiple system abnormalities

Abstract

Among 58,000 amniocenteses completed, our laboratories found one case of true cytogenetic trisomy 2 mosaicism in a fetus with multiple abnormalities. In contrast, 11 fetuses phenotypically normal at birth were found to have true trisomy 2 mosaicism in their chorionic villus cells among the 10,500 fetuses tested by chorionic villus sampling (CVS). In our single abnormal case, amniocentesis performed at 19 weeks after finding an elevated maternal serum AFP found two independent cultures with trisomy 2 karyotypes in 8 of 25 and 7 of 31 amniocytes, respectively. Although oligohydramnios was noted by ultrasound, the mother elected to continue the pregnancy. At 26 weeks the fetus had intrauterine growth retardation (IUGR), hydronephrosis, and cardiac abnormalities. When delivered by Cesarean section at 30 weeks, the infant had multiple anomalies and developed necrotizing enterocolitis and severe cholestasis. At 5 months coronal magnetic resonance imaging (MRI) displayed delayed myelination and abnormal brain morphology. The patient also exhibited significant growth failure and developmental delay. Although chromosomes were normal in blood, skin fibroblasts, and ascites fluid cells, 4 of 100 hepatic biopsy fibroblasts were 47,XY,+2. Molecular analysis excluded uniparental disomy (UPD) of chromosome 2 in the 46,XY cell line. This and other reports of rare phenotypically abnormal trisomy 2 mosaic fetuses identified by karyotyping amniocytes emphasizes the substantially higher fetal risk of abnormal development than when trisomy 2 is found only in chorionic villus cells.

Chromosomal abnormalities and copy number variations in fetal left‐sided congenital heart defects

“…Because amniocytes were the cells used for the initial diagnosis, this result was not caused by a confined placental mosaicism. This aberration is known to be associated with cardiac defects and multiple congenital malformations . Follow‐up is unavailable because the pregnancy was terminated without post‐mortem analysis.…”

Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH)

“…EFNB1 has important roles in migration of neural crest cells, a pathway proposed to be involved in CDH (Davy et al, 2004;Davy and Soriano, 2005;Arvanitis and Davy, 2008). A single report in the DGV finds the region encompassing the EFNB1 gene to be a rare variant in normal individuals (frequency <1%) (Shaikh et al, 2009 (Robinson et al, 1997;Sago et al, 1997;Mihci et al, 2009). In a recent report, Mihci et al describe a patient with mosaic trisomy 2 and displaying mental retardation, multiple congenital anomalies including diaphragmatic hernia, and dysmorphic features similar to Pallister-Killian syndrome (Mihci et al, 2009).…”

Trisomy 9 Mosaicism Diagnosed In Utero

“…In this case, the infant demonstrated mild FGR with a congenital diaphragmatic hernia. When a cytogenetic discrepancy between amniocytes and postnatal blood is observed, it is not rare for mosaic tissue to be confined to a specific organ [5, 7]. We failed to perform postnatal cytogenetic analysis on the other two cases which resulted in IUFDs.…”