Ring Chromosome 20 Syndrome and Epilepsy

Abstract

The ring chromosome 20 [r(20)] syndrome is a chromosomal disorder, characterized by refractory epilepsy, mild-to-moderate intellectual disability, and behavioral anomaly. In spite of structural chromosomal aberrations, malformations are often not recognized. In addition, neurological anomalies and abnormalities in brain magnetic resonance imagings are usually not detected. The epilepsy is refractory and mainly presents as atypical absence seizures or nocturnal frontal lobe seizures, with frequent episodes of nonconvulsive status epilepticus in typical cases. Ictal electroencephalograms performed during nonconvulsive status epilepticus episodes typically record spike wave discharges, superimposed with 2- to 3-Hz rhythmic slow waves predominantly in the frontal lesion. Since the r(20) syndrome was initially reported as a genetic syndrome in 1976, over 60 cases have been published to date. Most cases are sporadic, except four familial cases that have been previously reported. This syndrome is diagnosed only by karyotyping. Since epilepsy is the only symptom in most patients, genetic testing and diagnosis are usually delayed. In addition, patients usually exhibit mosaicism in lymphocytes, and the proportion of lymphocytes with the r(20) varies. Although some studies have evaluated the relationship between the phenotype and the proportion of lymphocytes with the r(20), no significant relationship has emerged. Ring chromosomes are usually formed by the fusion of each 20p and 20q telomere and cause the loss of both telomeres. Therefore, the r(20) syndrome is thought to be caused by haploinsufficiency of genes located on the telomeric regions of chromosome 20. However, in spite of showing typical symptoms of the r(20) syndrome, a patient in whom telomeres were not deleted has also been reported. Moreover, apart from the genes located on chromosome 20, two genes associated with epilepsy, KCNQ2 and CHRNA4, have also been located at p13ter and 13qter. Hence, the mechanism underlying seizure disorders in r(20) syndrome remains unknown. This review discusses the current knowledge about the genetic etiology of r(20) syndrome.