Monosomy 21 seen in live born is unlikely to represent true monosomy 21: a case report and review of the literature

Abstract

We report a case of a neonate who was shown with routine chromosome analysis on peripheral blood lymphocytes to have full monosomy 21. Further investigation on fibroblast cells using conventional chromosome and FISH analysis revealed two additional mosaic cell lines; one is containing a ring chromosome 21 and the other a double ring chromosome 21. In addition, chromosome microarray analysis (CMA) on fibroblasts showed a mosaic duplication of chromosome region 21q11.2q22.13 with approximately 45% of cells showing three copies of the proximal long arm segment, consistent with the presence of a mosaic ring chromosome 21 with ring instability. The CMA also showed complete monosomy for an 8.8 Mb terminal segment (21q22.13q22.3). Whilst this patient had a provisional clinical diagnosis of trisomy 21, the patient also had phenotypic features consistent with monosomy 21, such as prominent epicanthic folds, broad nasal bridge, anteverted nares, simple ears, and bilateral overlapping fifth fingers, features which can also be present in individuals with Down syndrome. The patient died at 4.5 months of age. This case highlights the need for additional studies using multiple tissue types and molecular testing methodologies in patients provisionally diagnosed with monosomy 21, in particular if detected in the neonatal period.

Figure 1

(a) demonstrates the observed broad nasal bridge, anteverted nares, and prominent epicanthis folds, (b) simple ears, and (c) bilateral 5th finger clinodactyly.

Figure 2

The monosomy 21 cell line is not shown. (a) G-banded fibroblast karyotype showing the ring chromosome 21. (b) Metaphase FISH of cultured fibroblasts using the ETV6/RUNX1 probe set indicating the presence of a double ring, that is, 1 copy of RUNX1 on the normal chromosome 21 and 2 copies on the double ring chromosome 21. (c) Chromosome microarray using the Illumina HumanCoreExome v1 performed on cultured fibroblast showing a copy number (Log⁡ R) that is consistent with the presence of a monosomic cell line and cell lines with a ring and double ring chromosome 21. The 8.8 Mb terminal deletion is also indicated. The B-allele frequency also confirms the mosaic nature of this finding.