Abstracts

Rationale: Ring Chromosome 20 [r(20)] syndrome is a rare chromosomal disorder characterized by childhood-onset drug-resistant epilepsy, behavioral problems, and cognitive impairment. Diagnosis is confirmed by cytogenetic analysis. While most cases are sporadic, rarely familial transmission occurs Methods: We report on the clinical, electroencephalographic and genetic findings in familial r(20) syndrome in a mother and her daughter. Workup included routine EEG, video-EEG, cerebral magnetic resonance imaging (MRI), and genetic studies (conventional cytogenetics, fluorescence in situ hybridization [FISH], SNP-microarray analysis). Results: The mother, currently 24 years of age, was referred with drug-resistant epilepsy of unknown origin for further evaluation. She is the first of four children of healthy, non-consanguineous parents, without a family history of neurological disorders. Pregnancy was uneventful and developmental milestones were reached timely until the age of ten, when prolonged episodes with fear, and impaired responsiveness with or without mild tonic posturing of both arms started. Initial EEGs showed intermittent background slowing predominating over the frontal regions. Video-EEG showed frequent, mainly nocturnal episodes of NCSE lasting up to one hour. Neuropsychological testing revealed mild to moderate frontal-executive impairment, brain MRI was inconspicuous. Several AEDs were used without rendering the patient seizure-free. Due to moderate behavioral problems she did not obtain a certificate of secondary education.Her five-year-old daughter developed complex partial seizures at the age of two. Treatment with Oxcarbazepine was initiated and the child is seizure free since more than two years. Developmental milestones were timely achieved until now. So far, the child has no cognitive or behavioral problems. Interictal EEG showed mild intermittent generalized slow waves, MRI was normal. Based on the electro-clinical findings chromosome r(20) syndrome was suspected and confirmed by cytogenetic analysis. R(20) mosaicism [46,XX,r(20)/46,XX] was found in both, the mother and the daughter. The r(20) was present in 12% of peripheral T-lymphocytes in the mother and in 50% of the cells in the daughter, respectively. Further characterization by FISH showed that subtelomere and telomere-repetitive sequences are preserved on the r(20). SNP-microarray-analysis in the daughter showed no loss of euchromatin and excluded uniparental isodisomy of chromosome 20.The karyotype of the maternal grandparents and the mother's husband was normal (analysis of 100 metaphases each). Conclusions: 1. Conventional karyotyping is recommended in all patients with drug-resistant non-lesional epilepsy associated with behavioral/cognitive problems. 2. Familial transmission of r(20) mosaicism may be explained by an inherited instability of chromosome 20 leading either to a de novo reformation of the ring or opening of the ring in the second generation (Daber et al., 2012).