Tauber Maithe, Diene Gwenaelle, Mimoun Emmanuelle, Çabal-Berthoumieu Sophie, Mantoulan Carine, Molinas Catherine, Muscatelli F, Salles Jean Pierre
Centre de référence du syndrome de Prader-Willi, Hôpital des Enfants, CHU de Toulouse, Toulouse, France.
Front Horm Res. 2014;42:93-106. doi: 10.1159/000358317. Epub 2014 Apr 7.
Prader-Willi syndrome (PWS), first described in 1956, is considered as a paradigm of a neurodevelopmental disorder with severe and early obesity with hyperphagia and impaired satiety. The improved knowledge in the natural history and recent data on genetics offer new perspectives for understanding the metabolic and endocrine dysfunctions and possibly for treatment. Natural history of the disease has been described due to the early diagnosis performed in the first months of life and various nutritional phases have been described. In addition, there is clear evidence that the abnormal feeding behavior is included in the behavioral problems. Brain imaging studies have shown that some brain regions may be important in PWS. The role of SNORD116 gene cluster is detailed and its links with circadian rhythm and brain and hypothalamus development. Pathophysiology of the abnormal ghrelin levels and of OT dysfunction is documented. While no effect on appetite and weight regulation has been reported with ghrelin antagonists, OT has been shown to improve some of the behavioral problems in adults. We discuss our hypothesis of an abnormal ghrelin/OT/dopamine pathway which may explain the switch of nutritional phases and behavior. These new aspects offer an opportunity for therapeutic use and possible early intervention.
普拉德-威利综合征（PWS）于1956年首次被描述，被认为是一种神经发育障碍的范例，伴有严重的早期肥胖、食欲亢进和饱腹感受损。对其自然史的深入了解以及最近的遗传学数据为理解代谢和内分泌功能障碍以及可能的治疗提供了新的视角。由于在生命的最初几个月进行了早期诊断，该病的自然史已被描述，并且描述了各个营养阶段。此外，有明确证据表明异常的进食行为包含在行为问题中。脑成像研究表明，某些脑区在PWS中可能很重要。详细阐述了SNORD116基因簇的作用及其与昼夜节律以及大脑和下丘脑发育的联系。记录了胃饥饿素水平异常和催产素功能障碍的病理生理学。虽然胃饥饿素拮抗剂对食欲和体重调节没有影响，但催产素已被证明可以改善成年人的一些行为问题。我们讨论了胃饥饿素/催产素/多巴胺通路异常的假说，这可能解释营养阶段和行为的转变。这些新方面为治疗应用和可能的早期干预提供了机会。
