Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy

Tara L. Wenger, Randall A. Bly, Natalie Wu, Catherine M. Albert, Julie Park, Joseph Shieh, Jirat Chenbhanich, Carrie L. Heike, Margaret P. Adam, Irene Chang, Angela Sun, Danny E. Miller, Anita E. Beck, Deepti Gupta, Markus D. Boos, Elaine H. Zackai, David Everman, Shireen Ganapathi, Meredith Wilson, John ChristodoulouYuri A. Zarate, Cynthia Curry, Dong Li, Anne Guimier, Jeanne Amiel, Hakon Hakonarson, Richard Webster, Elizabeth J. Bhoj, Jonathan A. Perkins, John P. Dahl, William B. Dobyns

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1576-1591
Number of pages16
JournalAmerican Journal of Medical Genetics, Part A
Issue number7
StatePublished - Jul 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
We thank the individuals, families, and their referring physicians for their important contributions to this work, as well as Leslie Biesecker. The study was funded by the US National Institutes of Health under NHLBI or NINDS grant numbers 1R01HL130996 and 5R01NS050375 to W. B. D. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources. We would also like to thank Erik Stuhaug and Eden Palmer for photography. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program.

Publisher Copyright:
© 2020 Wiley Periodicals, LLC.


  • Kosaki overgrowth syndrome
  • Penttinen syndrome
  • fusiform aneurysm
  • imatinib
  • myofibromatosis

PubMed: MeSH publication types

  • Case Reports
  • Journal Article
  • Research Support, N.I.H., Extramural


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