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Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

Jirat Chenbhanich1, Yan Hu2, Steven Hetts3

  • 1Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California, USA.

American Journal of Medical Genetics. Part A
|March 8, 2021
PubMed

Insights

Activating platelet-derived growth factor receptor β (PDGFRB) variants cause overgrowth and premature aging syndromes. This study highlights PDGFRB variants in patients with aneurysms, emphasizing the need for genetic testing and vascular imaging.

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Developmental Biology

Background:

  • Activating variants in the platelet-derived growth factor receptor β (PDGFRB) gene are linked to Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome.
  • A specific mosaic PDGFRB variant (c.1685A>G p.(Tyr562Cys)) has been associated with a phenotype including fusiform aneurysms.
  • Limited research exists on the vascular manifestations and mosaicism associated with PDGFRB variants.

Purpose of the Study:

  • To describe the clinical features of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant.
  • To investigate the association between PDGFRB-activating variants and vascular phenotypes, particularly aneurysms.
  • To review existing literature for similar cases and consolidate knowledge on PDGFRB-related conditions.

Main Methods:

  • Next-generation sequencing-based genetic testing was used to identify the PDGFRB variant in two patients.
  • Clinical characteristics of the patients were documented.
  • A literature search was conducted to identify additional patients with aneurysms and phenotypes related to PDGFRB-activating variants.

Main Results:

  • Two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant were identified, with one presenting intracranial fusiform aneurysm.
  • A literature review revealed eight additional patients with aneurysms and phenotypes consistent with PDGFRB-activating variants.
  • Conditions associated with PDGFRB-activating variants share overlapping features such as overgrowth, premature aging of the skin, and vascular malformations including aneurysms.

Conclusions:

  • PDGFRB-activating variants are associated with a spectrum of conditions including overgrowth, premature aging, and progressive vascular malformations like aneurysms.
  • Germline and/or somatic PDGFRB gene testing is recommended for individuals presenting with related phenotypes.
  • Comprehensive vascular imaging (arterial tree and echocardiography) and follow-up imaging are crucial for managing these progressive conditions.
Keywords:
Kosaki syndromePDGFRBPenttinen syndromeaneurysminfantile myofibromatosisovergrowth syndrome

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