A prenatal diagnosis of mosaic trisomy 5 reveals a postnatal complete uniparental disomy of chromosome 5 with multiple congenital anomalies

Abstract

Mosaic trisomy 5 is a very rare condition in liveborns, with few cases reported in the last four decades. There are some reports of prenatally diagnosed mosaic trisomy 5 resulting in phenotypically normal offspring, suggesting a low level of mosaicism, but there are also reports associated with multiple congenital anomalies, cardiovascular malformations, and intrauterine growth restriction. We report an infant male diagnosed with mosaic trisomy 5 (5/15 cells) via amniocentesis. The patient was subsequently found to have uniparental disomy 5 (UPD5) by postnatal chromosome microarray, but high-resolution chromosome analysis on peripheral blood did not identify trisomy 5. Dysmorphic features included a tall forehead with low anterior hairline, hypertelorism, low-set ears, and a prominent nose and midface. Other anomalies included bilateral bifid thumbs, hypospadias, a perineal fistula, unilateral multicystic kidney, and decreased subcutaneous fat with loose skin. He had complex congenital heart disease consisting of ventricular and atrial septal defects and polyvalvular defects. The patient died at age one after a prolonged admission. We add this case to the literature with the added benefit of data from a postnatal microarray, which was not available in other cases, to broaden the phenotype of mosaic trisomy 5 and UPD5.With the current available technology, we stress the importance of postnatal genetic testing to confirm prenatal cytogenetic findings in order to further define such phenotypes. This will provide the most accurate information and counseling to affected families.

VACTERL phenotype with mosaic trisomy 5 and uniparental disomy 5

“…Our patient and that reported by Reittinger et al () support expanding the phenotypic spectrum of mTri5/UPD5 to include VACTERL. Although the mechanism responsible for this genotype–phenotype association remains to be determined, UPD5 may be important.…”

“…As discussed by Reittinger et al (), mTri5/UPD5 probably results from postzygotic rescue of trisomy 5, leading to two abnormal cell lines: one with trisomy 5 and one with UPD5. Malformations in this genetic context are most likely due to mosaic trisomy 5, UPD5, or perhaps interactions between the two abnormal cell populations.…”

“…Reittinger, Helm, Boles, Gadi, and Schrier Vergano () recently reported a fascinating patient with mosaic trisomy 5 and uniparental disomy 5 (UPD5) who presented with multiple congenital anomalies. They summarize literature related to eight previously reported liveborn patients with mosaic trisomy 5 and five previously reported patients with UPD5, none of whom shared similar phenotypic features to their patient.…”

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).…”

Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism

“…Currently, seven cases of mosaic trisomy of chromosome 5 may be found in the available literature. It is suggested to be one of the most severe forms of mosaic autosomal trisomy [40,94].…”