De Leersnyder Hélène
Department of Genetics, Robert Debré Hospital, 48 boulevard Sérurier, 75019 Paris, France.
Trends Endocrinol Metab. 2006 Sep;17(7):291-8. doi: 10.1016/j.tem.2006.07.007. Epub 2006 Aug 4.
Smith-Magenis syndrome (SMS) is a mental retardation syndrome with distinctive behavioral characteristics, dysmorphic features and congenital anomalies ascribed to an interstitial deletion of chromosome 17p11.2. Severe sleep disturbances and maladaptative daytime behavior have been linked to an abnormal circadian secretion pattern of melatonin, with a diurnal instead of nocturnal secretion of this hormone. SMS provides a demonstration of a biological basis for sleep disorder in a genetic disease. Considering that clock genes mediate the generation of the circadian rhythm, haploinsufficiency for a circadian system gene, mapping to chromosome 17p11.2 might cause the inversion of the melatonin circadian rhythm in SMS. The disorder of circadian timing in SMS might also affect the entrainment pathway (retinohypothalamic tract), pacemaker functions (suprachiasmatic nucleus) or synthesis and release of melatonin by the pineal gland. Elucidating pathophysiological mechanisms of behavioral phenotypes in genetic disease can provide an original therapeutic approach in SMS: blockade of endogenous melatonin production during the day combined with exogenous melatonin administration in the evening.
史密斯-马吉尼斯综合征（SMS）是一种智力发育迟缓综合征，具有独特的行为特征、畸形特征和先天性异常，归因于17号染色体p11.2区域的间质性缺失。严重的睡眠障碍和适应不良的白天行为与褪黑素昼夜分泌模式异常有关，即这种激素在白天而非夜间分泌。SMS为遗传疾病中的睡眠障碍提供了生物学基础的例证。鉴于生物钟基因介导昼夜节律的产生，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中褪黑素昼夜节律的倒置。SMS中昼夜节律定时的紊乱也可能影响输入通路（视网膜下丘脑束）、起搏器功能（视交叉上核）或松果体合成和释放褪黑素。阐明遗传疾病中行为表型的病理生理机制可为SMS提供一种原创性治疗方法：白天阻断内源性褪黑素的产生，同时在晚上给予外源性褪黑素。
