Daber Robert D, Conlin Laura K, Leonard Laura D, Canevini Maria P, Vignoli Aglaia, Hosain Syed, Brown Lawrence W, Spinner Nancy B
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 1007A Abramson Research Center, 3615 Civic Center Boulevard, The Children's Hospital of Philadelphia, PA 19104, USA.
Eur J Med Genet. 2012 May;55(5):381-7. doi: 10.1016/j.ejmg.2012.02.004. Epub 2012 Feb 22.
Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems and mild to severe cognitive impairment. Facial dysmorphism or other congenital malformations are rarely reported making it difficult to diagnose the syndrome based on clinical findings alone. Therefore, diagnosis requires cytogenetic testing. More than 100 cases have been published since the initial report in 1972. In some patients, the ring (20) is found in all cells analyzed and in these cases, the ring is almost always accompanied by deletions of 20pter and/or 20qter. However, in the majority of cases the ring is present in only a proportion of cells, with two normal 20's in the remaining cells (mosaicism), and in these cases, no deletions of chromosome 20 have been observed. Patients with supernumerary r(20) chromosomes have also been identified, but these individuals do not generally have seizures and are not discussed in this review. Characterization by fluorescence in situ hybridization and array-based analysis has shed insight into the molecular composition and possible mechanisms of ring formation, in both the mosaic and non-mosaic patients. The age of onset of seizures correlates with the percentage of cells with the ring in mosaic patients. While the underlying etiology of the phenotype is still not understood, evidence is accumulating which suggests the deletion of candidate genes on chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal microarray analysis is recommended for diagnosis of this syndrome, as the mosaic cases do not have copy number alterations and are therefore not identified by array-based analysis.
20号环状染色体综合征是一种罕见的染色体疾病，其特征为顽固性癫痫，在清醒和睡眠时均有发作，伴有行为问题以及轻度至重度认知障碍。面部畸形或其他先天性畸形很少被报道，这使得仅根据临床症状难以诊断该综合征。因此，诊断需要进行细胞遗传学检测。自1972年首次报道以来，已发表了100多例病例。在一些患者中，在所有分析的细胞中都发现了环状（20）染色体，在这些病例中，环状染色体几乎总是伴有20号染色体短臂和/或长臂的缺失。然而，在大多数病例中，环状染色体仅存在于一部分细胞中，其余细胞中有两条正常的20号染色体（嵌合体），在这些病例中，未观察到20号染色体的缺失。也已鉴定出具有额外r(20)染色体的患者，但这些个体一般没有癫痫发作，本文对此不作讨论。通过荧光原位杂交和基于芯片的分析进行的特征分析，使我们对嵌合体和非嵌合体患者环状染色体的分子组成和形成的可能机制有了深入了解。在嵌合体患者中，癫痫发作的发病年龄与含有环状染色体的细胞百分比相关。虽然该表型的潜在病因仍不清楚，但越来越多的证据表明，20号染色体上候选基因的缺失并非病因所在。对于该综合征的诊断，建议进行细胞遗传学分析而非染色体微阵列分析，因为嵌合体病例没有拷贝数改变，因此基于芯片的分析无法识别。
