Division of Human Genetics, Children's Hospital of Philadelphia.
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania.
Curr Opin Pediatr. 2023 Dec 1;35(6):620-630. doi: 10.1097/MOP.0000000000001298. Epub 2023 Oct 4.
This review will focus on the current knowledge of the diagnosis and management of overgrowth syndromes with specific focus on mosaic conditions and treatment strategies.
With the implementation of massively parallel sequencing, the genetic etiology of many classically described overgrowth syndromes have been identified. More recently, the role of mosaic genetic changes has been well described in numerous syndromes. Furthermore, the role of imprinting and methylation, especially of the 11p15 region, has been shown to be instrumental for growth. Perhaps most importantly, many overgrowth syndromes carry an increased risk of neoplasm formation especially in the first 10 years of life and possibly beyond. The systematic approach to the child with overgrowth will aide in timely diagnosis and efficiently align them with appropriate screening strategies. In some cases, precision medical interventions are available to target the perturbed growth signaling pathways.
The systematic approach to the child with overgrowth aids in the standardization of the diagnostic pathway for these young patients, thereby expediting the diagnostic timeline, enabling rigorous monitoring, and delivering tailored therapeutic interventions.
本篇综述将重点关注过度生长综合征的诊断和管理的最新知识，尤其侧重于嵌合体疾病和治疗策略。
随着大规模平行测序的应用，许多经典描述的过度生长综合征的遗传病因已被确定。最近，嵌合遗传改变在许多综合征中的作用也得到了很好的描述。此外，印迹和甲基化（尤其是 11p15 区域）的作用对于生长至关重要。也许最重要的是，许多过度生长综合征增加了肿瘤形成的风险，尤其是在生命的前 10 年，甚至可能更长时间。对过度生长患儿进行系统评估有助于及时诊断，并为其制定相应的筛查策略。在某些情况下，可以采用精准医疗干预措施来靶向受干扰的生长信号通路。
对过度生长患儿进行系统评估有助于规范这些年轻患者的诊断路径，从而缩短诊断时间，加强监测，并提供针对性的治疗干预。
