環状20番染色体症候群

Ring chromosome 20 (ring 20) is a rare genetic condition usually presenting as developmental and epileptic encephalopathy. The disease is caused by fusion of the long and short arms of chromosome 20. Patients are symptomatic even if there is no loss of genetic material. Epilepsy in ring 20 is usually drug-resistant, with seizures often significantly debilitating and severely impacting quality of life. We assembled a taskforce of clinician-scientists with expertise in ring 20, as well as caregivers of individuals with ring 20. We then reviewed published literature on ring 20 with a focus on management with the aim of developing recommendations for the treatment of this disorder. Our review found that there are very few high-quality data available to guide treatment in ring 20. The majority of publications are individual case reports or small case series. Based on these limited data, as well as personal experience, we recommend the following. (1) The care team should be multidisciplinary and include at least an epileptologist and allied health specialists (e.g., speech therapist, occupational therapist, physiotherapist, psychologist); (2) patients and families should be referred for genetic counseling; (3) if patients are diagnosed with epilepsy, they and their families should be counseled that seizures are likely to be drug-resistant and life-long; (4) as there is a high incidence of non-convulsive status epilepticus (NCSE), there should be a low threshold for video-EEG monitoring if patients have a change in behavior or level of consciousness; (5) initial epilepsy treatment should be with an oral anti-seizure medication; (6) home rescue medication should be considered given the risk for prolonged seizures and NCSE; (7) for patients with drug-resistant epilepsy, ketogenic diet, vagus nerve stimulation, or deep brain stimulation could all be considered; and (8) caregiver burnout and stress should be screened for and supports provided.

Ring chromosome 20 (r[20]) syndrome is a rare epilepsy-associated chromosomal disorder often accompanied by intellectual disability and psychiatric symptoms. It lacks distinctive physical features and typically exhibits normal brain imaging; therefore, its diagnosis is frequently delayed, especially when clinicians are unfamiliar with it. Nonconvulsive status epilepticus (NCSE), a hallmark of this syndrome, can be overlooked even by epilepsy specialists, who interpret it as a psychiatric symptom, particularly in patients with limited expressive capacity. A 42-year-old woman with a long-standing history of drug-resistant epilepsy and behavioral symptoms was ultimately diagnosed with r(20) syndrome. She developed tonic seizures and fear episodes at age 6 and was diagnosed with epilepsy. After age 11, drug-resistant NCSE emerged and was not clearly identified as status epilepticus; it was considered to involve impaired awareness seizures and psychiatric symptoms. At age 41, perampanel (PER) was initiated, triggering aggressive behavior and new backward-falling episodes, further complicating her clinical presentation. Video electroencephalogram (EEG) confirmed NCSE, and chromosomal analysis identified r(20). After PER discontinuation, aggression and backward-falling episodes resolved. Lacosamide was introduced, reducing the frequency of NCSE from several daily episodes to 2-3 per week. This case underscores the diagnostic challenges of r(20) syndrome and the risk of misdiagnosing NCSE as a psychiatric illness. Additionally, PER may exacerbate psychiatric symptoms in r(20) cases with intellectual disability. Precise seizure classification and confirmation by ictal EEG, along with integrated neuropsychiatric care, are essential for accurate diagnosis and effective management.

Objective: To analyze the clinical features and diagnostic process of ring chromosome syndrome. Methods: Clinical data of 9 children with ring chromosome syndrome who were treated at the Children's Medical Center of Peking University First Hospital from September 2009 to May 2025, were summarized and analyzed in a case series study. The data included clinical manifestations, types of epileptic seizures, genetic testing, treatment outcomes, and follow-up results, et al. Results: Among the 9 children with ring chromosome syndrome, there were 6 girls and 3 boys, including 4 children with ring chromosome 20 syndrome, 3 children with ring chromosome 14 syndrome, and 1 child each with ring chromosome 13 and 17 syndrome. All 9 children had de novo chromosomal variations. Among them, 3 children of ring chromosome 20 syndrome were mosaic, and the remaining 6 children were non-mosaic. All 9 children exhibited diverse clinical features, especially those with ring chromosome 20 syndrome, which presented with specific manifestations. The 4 children with ring chromosome 20 syndrome all had acute epileptic seizures as the initial symptom, with onset ages of 67, 39, 17, and 96 months, and all had focal seizures. One child with ring chromosome 20 syndrome had non-convulsive status epilepticus. Development of all 4 children with ring chromosome 20 syndrome was normal before seizure onset, but 3 children showed regression after onset. No physical deformities were observed in 4 children with ring chromosome 20 syndrome, and 2 children were misdiagnosed, 3 children underwent whole exome sequencing and copy number variation analysis in their families, with no abnormalities detected. All 4 children with ring chromosome 20 syndrome were diagnosed through chromosomal karyotype analysis, the intervals between onset and diagnosis were 2, 81, 19 and 13 months, respectively. Follow-up showed that epileptic seizures were not controlled in all 4 children with ring chromosome 20 syndrome. The other 5 children were characterized by developmental delay as the initial symptom, followed by epileptic seizures between 3 and 24 months of age. Developmental regression of the other 5 children did not occur after onset, 2 of them had microcephaly, and 3 had wide-set eyes. No misdiagnoses were reported in these 5 children, and the intervals between onset and diagnosis were 7, 3, 55, 3, and 106 months, respectively. Follow-up showed that epileptic seizures were controlled in these 5 children. Conclusions: Ring chromosome 20 syndrome typically manifest with epilepsy as the initial symptom and are refractory to drug treatment, their early development is entirely normal. Ring chromosome 13, 14, and 17 syndrome are characterized by developmental delay from an early age, followed by the onset of epileptic seizures, which are easily controlled. Conventional whole-exome sequencing and copy number variation analysis in families rarely detect ring chromosome abnormalities. Early chromosomal karyotype analysis is essential for the diagnosis of ring chromosome syndrome.

Ring chromosome 20 syndrome (r (20)) is a rare genetic disorder characterized by drug-resistant epilepsy, cognitive impairment, and behavioral changes, often manifesting with non-convulsive status epilepticus (NCSE). We report a unique case of a 38-year-old woman with r (20) and recurrent NCSE, demonstrating a novel and striking electro-clinical correlation. Continuous video-EEG monitoring revealed distinct, alternating electro-clinical phases, with NCSE manifesting as continuous spike-wave during sleep (CSWS)-like patterns. Notably, the onset of REM sleep was consistently associated with a near-complete resolution of epileptiform abnormalities, followed by seizure-free awakening from REM. Intriguingly, the introduction of melatonin (4 mg/day) appeared to facilitate the attainment of REM sleep and was associated with a gradual reduction in NCSE frequency. This observation highlights the potential critical role of the neurophysiological state of REM sleep - characterized by cholinergic predominance and active GABAergic inhibition - in modulating and potentially suppressing the aberrant cortical excitability underlying NCSE in r (20). We hypothesize that the disrupted sleep architecture in r (20) may contribute to NCSE vulnerability, and that enhancing REM sleep dynamics could counteract this predisposition. The observed benefit of melatonin, potentially acting on MT1 receptors, warrants further investigation into targeted interventions aimed at normalizing sleep architecture, particularly REM sleep, as a novel therapeutic strategy for managing drug-resistant epilepsy and NCSE in r (20). This case underscores the importance of REM sleep in the context of epilepsy in r (20) and calls for future studies to elucidate the underlying mechanisms and confirm these findings in larger cohorts.

PURPOSE: Ring chromosome 20 is a rare genetic syndrome characterized by epilepsy, intellectual disability, and other neurodevelopmental abnormalities. Seizures in ring chromosome 20 are often drug-resistant and debilitating. For patients with drug-resistant epilepsy, non-medical options are often considered; however, the efficacy of these interventions is not well-understood. In this retrospective case series, we investigated the utility of vagus nerve stimulation in people with ring chromosome 20. METHODS: Patients were identified from our research/clinical databases, and with the assistance of a patient support group. Patients and/or caregivers were interviewed by phone or video teleconference. Data collected included demographics, epilepsy characteristics, and response to medical and non-medical treatments, including vagus nerve stimulation. RESULTS: Fourteen patients were included in the study. 11/14 reported some improvement in epilepsy following vagus nerve stimulator implantation, including five with reduced seizure frequency, three with shorter seizure duration, three with reduction or elimination of non-convulsive status epilepticus or specific seizure types, two with reduced need for rescue medication, and two shorter post-ictal signs/symptoms. Two patients were reported to have improved cognitive function and one a reduction in aggressive behaviour. CONCLUSION: Overall, vagus nerve stimulation appears to be an effective treatment for some patients with ring chromosome 20 and drug-resistant epilepsy.