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. 1. Introduction Apparent full monosomy 21 has been reported in ten cases in the pre- and postnatal settings (excluding early pregnancy loss), with most cases being lethal in utero [1–14]. However, many of these cases were reported when cytogenetic techniques were limited and often only single tissues were investigated. Clinical features of monosomy 21 include severe Intrauterine Growth Retardation (IUGR), ear anomalies, clinodactyly (5th finger), seizures, and anteverted nares. Cases of monosomy 21 reported in live born, as was the provisional diagnosis in this case, are unlikely to represent true full monosomy 21. The presence of a second undetected cell line being the most likely explanation for pregnancies reaching term. The presence of a ring chromosome 21, due to their mitotic instability and propensity for tissue limited mosaicism, provides a plausible explanation for some of the previously reported cases of full monosomy 21. In particular, when detected in the neonatal setting. The associated phenotype in patients with mosaic ring chromosome 21 with monosomy 21 is varied. Features range from apparently normal individuals [15] through to individuals with dysmorphic features and congenital abnormalities [16]. The severity of the phenotype
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