Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings.
Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings.
复制标题
DOI：
10.1007/s40618-015-0312-9
复制
发表时间：
2015-12
影响因子：
5.4
通讯作者：
Cataletto ME
中科院分区：
文献类型：
--
作者：
Angulo MA;Butler MG;Cataletto ME
Prader-Willi综合征（PWS）是一种由父系遗传的染色体15q11.2-q13区域基因表达缺失引起的多系统复杂遗传疾病。PWS有三种主要的遗传亚型：父亲15q11-q13缺失（65 - 75%的病例），母亲单亲二体15（20 - 30%的病例）和印迹缺陷（1 - 3%）。DNA甲基化分析是唯一能够诊断PWS所有三个分子遗传类别并将PWS与Angelman综合征区分开来的技术。临床表现随年龄的变化而变化，在婴儿期表现为低张力和吸力差导致发育不全。随着个体年龄的增长，其他特征，如身材矮小，过度增重的食物寻求，发育迟缓，认知障碍和行为问题变得明显。该表型可能是由于下丘脑功能障碍引起的，下丘脑功能障碍导致嗜食、体温不稳定、高痛阈、嗜睡和多种内分泌异常，包括生长激素和促甲状腺激素缺乏、性腺功能减退和中枢性肾上腺功能不全。肥胖及其并发症是PWS发病和死亡的主要原因。对文献进行了广泛的回顾，并在临床实践的背景下进行了解释，并经常向转诊医生和家属提出问题，包括PWS的病因和诊断的临床、遗传学和内分泌方面的发现的现状。关于Prader-Willi综合征患者早期诊断和治疗的最新信息对所有医生都很重要，并且有助于预测和管理或改变与这种罕见的肥胖相关疾病相关的并发症。
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion (65–75 % of cases), maternal uniparental disomy 15 (20–30 % of cases), and imprinting defect (1–3 %). DNA methylation analysis is the only technique that will diagnose PWS in all three molecular genetic classes and differentiate PWS from Angelman syndrome. Clinical manifestations change with age with hypotonia and a poor suck resulting in failure to thrive during infancy. As the individual ages, other features such as short stature, food seeking with excessive weight gain, developmental delay, cognitive disability and behavioral problems become evident. The phenotype is likely due to hypothalamic dysfunction, which is responsible for hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency. Obesity and its complications are the major causes of morbidity and mortality in PWS. An extensive review of the literature was performed and interpreted within the context of clinical practice and frequently asked questions from referring physicians and families to include the current status of the cause and diagnosis of the clinical, genetics and endocrine findings in PWS. Updated information regarding the early diagnosis and management of individuals with Prader-Willi syndrome is important for all physicians and will be helpful in anticipating and managing or modifying complications associated with this rare obesity-related disorder.