Abstract
Ring chromosome 20 [r(20)] syndrome is a rare condition characterized by a non-supernumerary ring chromosome 20 replacing a normal chromosome 20. It is commonly seen in a mosaic state and is diagnosed by means of karyotyping. r(20) syndrome is characterized by a recognizable epileptic phenotype with typical EEG pattern, intellectual disability manifesting after seizure onset in otherwise normally developing children, and behavioral changes. Despite the distinctive phenotype, many patients still lack a diagnosis—especially in the genomic era—and the pathomechanisms of ring formation are poorly understood. In this review we address the genetic and clinical aspects of r(20) syndrome, and discuss differential diagnoses and overlapping phenotypes, providing the reader with useful tools for clinical and laboratory practice. We also discuss the current issues in understanding the mechanisms through which ring 20 chromosome causes the typical manifestations, and present unpublished data about methylation studies. Ultimately, we explore future perspectives of r(20) research. Our intended audience is clinical and laboratory geneticists, child and adult neurologists, and genetic counselors.
Highlights
Ring chromosomes (RCs) are rare genetic events that result from an intra-chromosomal fusion (1)
The ring chromosomes have been reported in different tissues and have been seen prenatally in both the amniotic fluid and chorionic villi samples, as well as in postnatal peripheral blood, bone marrow, and fibroblasts (Supplementary Table 1)
Ring chromosome 20 syndrome is a rare and likely underdiagnosed condition characterized by a distinctive epileptic phenotype
Summary
Ring chromosomes (RCs) are rare genetic events that result from an intra-chromosomal fusion (1). In these patients the r(20) did not show telomeric repeats at the ring junction and was characterized by microdeletions of at least one variably-sized subtelomeric sequence with no recurrent breakpoints (10). In mosaic patients the r(20) maintained intact subtelomeric and telomeric sequences, and no genomic imbalances of the chromosome were detected (Figures 1h,i,l) Based on this evidence, post-zygotic telomere fusion is thought to be the most probable mechanism for ring formation (Table 1). In addition to the haplotype analysis, Giardino et al exploited FISH analysis using a 20-specific alphoid probe able to visualize signal intensities that are dependent on the different number of alphoid repeats The application of this tool allowed to differentiate the linear and the r(20) chromosomes in some patients carrying this centromeric polymorphism (12) (Figures 1f,g). The percentage of r(20) in each category is indicated above each column
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