De Leersnyder Hélène, Claustrat Bruno, Munnich Arnold, Verloes Alain
Department of Genetics, Hospital Robert Debré, 75019 Paris, France.
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):88-91. doi: 10.1016/j.mce.2006.03.043. Epub 2006 May 24.
Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome, caused by interstitial deletion of chromosome 17p11.2. The SMS phenotype include distinctive facial features, developmental delay and neurobehavioral abnormalities. The patients present major sleep disturbances ascribed to a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Treatment with morning beta-blockers and evening melatonin reinstated a normally timed melatonin circadian rhythm, improved daytime behavior and restored normal sleep habits, resulting in a greatly improved quality of life for both SMS patients and their family. SMS is the demonstration of biological basis for sleep disorder in a genetic disease. Considering that clock genes mediate generation of circadian rhythms, we suggest that haploinsufficiency for a circadian system gene mapping to chromosome 17p11.2 may cause the inversion of circadian rhythm in SMS.
史密斯-马吉尼斯综合征（SMS）是一种临床上可识别的邻接基因综合征，由17号染色体p11.2区域的间质缺失引起。SMS的表型包括独特的面部特征、发育迟缓以及神经行为异常。患者存在严重的睡眠障碍，这归因于褪黑素昼夜节律的相位偏移以及该激素反常的日间分泌。早晨使用β受体阻滞剂和晚上使用褪黑素进行治疗可恢复正常定时的褪黑素昼夜节律，改善日间行为并恢复正常睡眠习惯，从而极大地提高了SMS患者及其家人的生活质量。SMS证明了遗传疾病中睡眠障碍的生物学基础。鉴于生物钟基因介导昼夜节律的产生，我们认为定位于17号染色体p11.2区域的昼夜节律系统基因单倍剂量不足可能导致SMS患者昼夜节律的倒置。
