Abstract
BACKGROUND AND OBJECTIVES: Ring 20 syndrome is a rare childhood-onset neurodevelopmental disorder caused by a postzygotic event leading to a structural change in the 20th chromosome. Next-generation sequencing (NGS) does not identify an abnormality in the most common mosaic form. Through a systematic review of the literature, we sought to identify clinically distinct characteristics that would trigger an order for a karyotype, which is the only definitive diagnostic test for this condition. METHODS: A systematic literature review was performed reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed and Web of Science were searched from inception through January 8, 2025. Included studies reported on mosaic ring 20 syndrome. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. RESULTS: A total of 70 publications reporting on 148 patients were included. Our review clearly reveals a distinct set of signs that should alert the informed neurologist to order a karyotype analysis at the first evaluation because it is currently the only method to properly diagnose this condition. Over 90% of cases which mention the seizure type describe multiply recurrent nonconvulsive status epilepticus. Patients generally do not have dysmorphia and are developing normally over the average of 7 years before seizure onset. The diagnosis of mosaic ring 20 syndrome should be considered in the setting of childhood-onset treatment-resistant epilepsy, particularly in the absence of focal abnormalities on brain MRI abnormalities, distinctive EEG findings, and pathogenic variants on short-read NGS. DISCUSSION: The diagnosis of mosaic ring 20 syndrome is via karyotype analysis. The current lag time from seizure onset to definitive diagnosis is 7.7 years. More widespread recognition of the distinctive clinical features of mosaic ring 20 syndrome should help shorten the diagnostic delay for affected individuals.