Ring Chromosome 20 Syndrome: Genetics, Clinical Characteristics, and Overlapping Phenotypes

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issues in understanding the mechanisms through which ring 20 chromosome causes the typical manifestations, and present unpublished data about methylation studies.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.

Additional Evidence for Neuropsychiatric Manifestations in Mosaic Trisomy 20: A Case Report and Brief Review

“…Along with numerical chromosome anomalies, such as mosaicism, structural anomalies of the chromosome 20, including ring chromosome [45], deletion of the short arm [46], microduplication within the short arm [47], and microdeleletion of the long arm [48], have also been associated with alterations in several body systems and functions as well as neurocognitive difficulties and neuropsychiatric features. Commonly reported behavioral manifestations include developmental delay, intellectual disability, sensory processing disorder, poor motor coordination, impaired speech and executive abilities, apathy or hyperactivity, loss of social skills and poor emotional regulation, obsessive behavior, psychosis, and autistic features.…”

Epilepsy genetics: a practical guide for adult neurologists

“…Onset of seizures can be preceded by marked nocturnal hallucinations and behavioural/developmental disturbance after the onset of seizures is common. 31 Ring formation on chromosome 20 -check karyotype. (figure 2)…”

Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies

“…Moreover, further genetic tests may be considered, as a way to unveil variants not detectable by comprehensive NGS techniques. Approaches such as karyotyping [diagnosis of ring chromosome 20 or 14 ( 63 ), as well as balanced translocations], nucleotide repeat expansions testing (diagnosis of familial cortical myoclonus syndrome, among others), sequencing of mitochondrial genome (if not included previously), sequencing of intronic or non-coding regions via WGS, or testing of epigenetic variants, could be considered. Testing of somatic mutations ( 64 ), some of them still only used in a research setting, might also be contemplated.…”