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Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2020 Jul; Vol. 182 (7), pp. 1576-1591. Date of Electronic Publication: 2020 Jun 05. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2020 Wiley Periodicals, LLC.)
- Subjects :
- Adolescent
Adult
Aneurysm genetics
Child
Female
Genetic Association Studies
Humans
Infant
Leukoencephalopathies drug therapy
Leukoencephalopathies genetics
Male
Myofibromatosis drug therapy
Myofibromatosis etiology
Myofibromatosis genetics
Pedigree
Protein Kinase Inhibitors therapeutic use
Imatinib Mesylate therapeutic use
Leukoencephalopathies etiology
Myofibromatosis congenital
Receptor, Platelet-Derived Growth Factor beta genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 182
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 32500973
- Full Text :
- https://doi.org/10.1002/ajmg.a.61615