Delineating the epilepsy phenotype of ring chromosome 20: A systematic literature review

Ring chromosome 20 is a rare genetic condition associated with childhood-onset intractable epilepsy, often with cognitive decline after seizure onset. To further elucidate the epilepsy phenotype, a systematic review of the literature was conducted.

The Preferred Report Items for Systematic Reviews and Meta-Analysis Guidelines (PRISMA) were followed. We systematically searched the MEDLINE, EMBASE, and Cochrane databases for research articles related to epilepsy and ring chromosome 20. We extracted information on epilepsy, comorbidities, electroencephalography, genetics, antiseizure medications (ASMs), and outcomes.

Seventy-one studies were included (192 patients), 40.4% (n = 67/166) were male. The median age at seizure onset was 7 years (IQR 4.9, 10). Focal seizures with impaired consciousness were most common (n = 94/187, 50.3%). Seventy-eight patient reports reported the presence of ictal fear, which was present in 56 cases (72%). Information on non-convulsive status epilepticus (NCSE) was available in 143 cases; 126 had experienced NCSE (88%). The median number of ASMs tried was 4 (2,7); most patients (80%, n = 92/115) were drug-resistant. There was a significant correlation between higher level of r(20) mosaicism in peripheral blood and earlier age of seizure onset (Spearman's rho = -0.51, p < 0.001). R(20) mosaicism percentage was also higher in patients with NCSE than without (p < 0.01), and in patients with intellectual disability versus no intellectual disability (p < 0.02).

Ring chromosome 20 is characterized by childhood-onset drug-resistant epilepsy, predominantly focal with ictal fear and NCSE. Higher percentage of r(20) mosaicism is associated with more severe phenotypes and may aid prognostication.