More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and late‐onset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response, including the first two reported infants with multicentric myofibromas treated with imatinib monotherapy and one with a recurrent p.Val665Ala (Penttinen) variant. Along with previously reported individuals, our cohort suggests infants and young children had few abnormal features, while older individuals had multiple additional features, several of which appeared to worsen with advancing age. Our analysis supports a diagnostic entity of a spectrum disorders due to activating variants in PDGFRB . Differences in reported phenotypes can be dramatic and correlate with advancing age, genotype, and to mosaicism in some individuals.

中文翻译：

---

激活 PDGFRB 中的变体会导致一系列对伊马替尼单一疗法有反应的疾病。

已报道超过 50 名个体具有受体酪氨酸激酶PDGFRB的激活变异体，根据临床特征分为孤立性肌纤维瘤、婴儿肌纤维瘤病、伴早衰和骨质减少的 Penttinen 综合征、Kosaki 过度生长综合征和梭形动脉瘤。尽管它们被描述为不同的临床实体，但对先前报告的回顾表明存在大量表型重叠。我们介绍了 12 名具有PDGFRB激活变异的患者的病例系列并回顾了文献。我们描述了五名PDGFRB患者激活其临床特征与多个诊断实体重叠的变体。来自一个大家庭的另外七名患者具有不同的表现力和迟发性疾病，包括成人发病特征和两名猝死患者。三名患者接受了伊马替尼治疗并产生了强烈而快速的反应，包括前两名报告的接受伊马替尼单一疗法治疗的多中心肌纤维瘤婴儿和一名患有复发性 p.Val665Ala (Penttinen) 变异的婴儿。与先前报告的个体一起，我们的队列表明婴幼儿几乎没有异常特征，而老年人有多种额外特征，其中一些似乎随着年龄的增长而恶化。我们的分析支持由于PDGFRB中的激活变异而导致的谱系障碍的诊断实体. 报告的表型差异可能是巨大的，并且与某些个体的年龄增长、基因型和镶嵌现象相关。