Prenatal diagnosis and postnatal follow‐up of a child with mosaic trisomy 22 with several levels of mosaicism in different tissues

Abstract

We report on the case of a patient with mosaic trisomy 22, who was diagnosed prenatally by amniocentesis during the 16(th) week of pregnancy. In the foetus, three trisomic clones were found out of the nine that were analyzed (the other six clones had a 46,XY karyotype). Cytogenetic analysis of cord blood during the 20(th) week of pregnancy showed a normal male karyotype; however, a placental biopsy that was performed at the same time showed 100% and 95% trisomic cells in the chromosomal analysis of direct and long-term cultures, respectively. A follow-up ultrasonographic examination excluded major congenital malformations and the abdominal and cranial circumferences were normal until the 24(th) week of pregnancy. At this point, a deflection of the growth curve occurred and the values were persistently below the 3(rd) centile until birth. After birth, karyotypic and fluorescent in situ hybridisation analyses performed on the fibroblasts of the neonate showed that 3-4% of the cell lines were trisomic, and studies using microsatellite markers showed normal allelic segregation, which excluded uniparental disomy. The period of postnatal follow-up was characterised by a significant growth deficit (height and head circumference were less than the 3(rd) centile) and by mental retardation. The present case is compatible with other earlier reports that showed that the levels of trisomy 22 are tissue-specific and are of little help in establishing the prognosis of the chromosomal abnormality.

A rare case of postnatal mosaic trisomy 12 with severe congenital heart disease and literature review

“…In the most recently published case report, Hu et al (Hu et al, 2020) suggested that culturing with Phytohemagglutinin (PHA), commonly used chemical in cell culture to stimulate T‐lymphocytes proliferation, could pose a selection pressure on the trisomic 12 cells as they are more susceptible to cell death. By searching the literature, we found similar phenomenon present in other autosomes such as chromosome 2, 5, 7, 16, 17, and 22, but not in chromosome 8, 9, and 15 (Chen et al, 2019; Daber et al, 2011; Hsu et al, 1997; Mazza et al, 2010; Reittinger et al, 2017). Interphase FISH or chromosomal microarray in uncultured lymphocytes; however, identified mosaic trisomies previously not identified by chromosome analysis (Cheung et al, 2007; Crowe et al, 1997; Luo et al, 2014).…”

Fetal aneuploidy screening by maternal plasma DNA sequencing: ‘False positive’ due to confined placental mosaicism

“…Most cases of trisomy 22 pregnancies result in early pregnancy losses, although rarely it may result in live births with multiple fetal anomalies or even with a morphologically normal baby . Mosaic trisomy 22 is also uncommon, which might affect the fetus or confined only to the placental tissues …”

“…It is well known that CPM is associated with fetal growth restriction. Almost all reported cases of mosaic 22, whether confined to the placenta or involving the fetus, were associated with significant growth restriction . Therefore, the knowledge of CPM allows closer appropriate follow up of fetal growth and wellbeing.…”

Trisomy 22 Mosaicism and Normal Developmental Outcome: Report of Two Patients and Review of the Literature

“…In its mosaic form trisomy 22 it is compatible with life. The level of mosaicism does vary in different tissues [Mazza et al, ]. In some patients analysis of peripheral lymphocytes yields normal karyotype which highlights the importance of testing other tissues when mosaic trisomy 22 is suspected [Lessick et al, ].…”