Elbracht Miriam, Prawitt Dirk, Nemetschek Rebekka, Kratz Christian, Eggermann Thomas
Human Genetics, University Hospital, RWTH Aachen, Aachen, Germany.
Kinder- und Jugendmedizin, Universitätsmedizin Mainz, Mainz, Germany.
Klin Padiatr. 2018 Apr;230(3):151-159. doi: 10.1055/a-0591-9479. Epub 2018 Apr 16.
Beckwith-Wiedemann syndrome (BWS) belongs to the group of imprinting disorders and is characterized by variable clinical features, including overgrowth, macroglossia, abdominal wall defect, neonatal hypoglycemia, body asymmetry and an increased risk for embryonal tumors. In the majority of cases, molecular alterations of the Imprinting Center (IC) regions in the chromosomal region 11p15.5 can be detected, and a correlation of single clinical features with specific genomic and epigenetic changes is obvious. Therefore, the detailed molecular diagnosis is a prerequisite for a precise prediction of the tumor risk and the tumor spectrum. Furthermore, it is the basis for a well-directed genetic counselling of the families. Despite a huge number of comprehensive studies based on a large number of cases, standardized diagnostic criteria and advices for therapeutic management were missing. In the following, the recently published first international consensus guidelines drafted by 41 experts in the field of BWS from 11 European countries and the USA are summarized. Patients support groups had been included as well. In total, 72 consented recommendations for clinical and molecular diagnosis as well as for the clinical management of BWS have been published. They refer both to patients with the classical BWS phenotype and to those with "atypical" phenotypes which are summarized as BWS spectrum (BWSp). A modified clinical scoring system is now suggested, which represents the basis to initiate molecular diagnostics. Therapeutic recommendations comprise the major clinical questions in BWS/BWSp, i. e. early monitoring of an increased tumor risk, treatment of the macroglossia and the abdominal wall defects, and therapeutic interventions for hypoglycemia. However, though there was a broad consensus on the majority of therapeutic interventions, discussions on tumor monitoring are foreseeable. Thus, prospective studies to evaluate the consensus guidelines and their use are planned.
贝克威思-维德曼综合征（BWS）属于印记紊乱疾病组，其临床特征多样，包括生长过度、巨舌症、腹壁缺损、新生儿低血糖、身体不对称以及胚胎性肿瘤风险增加。在大多数病例中，可检测到染色体区域11p15.5中印迹中心（IC）区域的分子改变，且单一临床特征与特定基因组和表观遗传变化之间的相关性明显。因此，详细的分子诊断是精确预测肿瘤风险和肿瘤谱的先决条件。此外，它也是为家庭提供针对性遗传咨询的基础。尽管基于大量病例进行了大量全面研究，但仍缺乏标准化的诊断标准和治疗管理建议。以下总结了最近由来自11个欧洲国家和美国的41位BWS领域专家起草的首个国际共识指南。患者支持团体也被纳入其中。总共发布了72条关于BWS临床和分子诊断以及临床管理的同意建议。这些建议既适用于具有经典BWS表型的患者，也适用于那些具有“非典型”表型（总结为BWS谱系（BWSp））的患者。现在建议采用一种改良的临床评分系统，这是启动分子诊断的基础。治疗建议涵盖了BWS/BWSp中的主要临床问题，即早期监测增加的肿瘤风险、治疗巨舌症和腹壁缺损以及对低血糖的治疗干预。然而，尽管在大多数治疗干预措施上达成了广泛共识，但关于肿瘤监测的讨论仍可预见。因此，计划开展前瞻性研究以评估共识指南及其应用。
