Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California, USA.
Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
Am J Med Genet A. 2021 May;185(5):1430-1436. doi: 10.1002/ajmg.a.62126. Epub 2021 Mar 8.
Activating variants in the platelet-derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next-generation sequencing-based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB-activating variants through literature search. The conditions caused by PDGFRB-activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant-related phenotypes are present. Whole-body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6- to 12-month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.
血小板衍生生长因子受体 β 基因 (PDGFRB) 中的激活变体与 Kosaki 过度生长综合征、婴儿肌纤维瘤病和 Penttinen 早衰综合征有关。最近描述的伴有梭形动脉瘤的表型与镶嵌性 PDGFRB c.1685A>G p.(Tyr562Cys) 变异有关。然而，很少有报道检查 PDGFRB 变体的血管表型和镶嵌效应。我们描述了通过下一代测序基因检测发现的两名复发性镶嵌性 PDGFRB p.(Tyr562Cys) 变异患者的临床特征。我们观察到一名患者颅内梭形动脉瘤，并通过文献检索发现了另外 8 名患有动脉瘤和与 PDGFRB 激活变体相关的表型的患者。由 PDGFRB 激活变体引起的病症具有重叠的特征，包括过度生长、过早衰老的皮肤和血管畸形，包括动脉瘤。动脉瘤是进行性的，如果没有成功的干预，可能会导致发病率和死亡率。当存在与 PDGFRB 激活变体相关的表型时，应获得 PDGFRB 基因的种系和/或体细胞检测。诊断后应推荐进行全身动脉树成像和超声心动图检查。在检测后 6 至 12 个月内重复进行影像学研究是合理的。最后，需要进一步评估激酶抑制剂在该患者人群中的有效性和安全性。
