Review of familial cerebral cavernous malformations and report of seven additional families

Ivo J. H. M. de Vos*, Maaike Vreeburg, Ger H. Koek, Maurice A. M. van Steensel

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

22 Citations (Web of Science)

Abstract

Cerebral cavernous malformations are vascular anomalies of the central nervous system characterized by clusters of enlarged, leaky capillaries. They are caused by loss-of-function mutations in KRIT1, CCM2, or PDCD10. The proteins encoded by these genes are involved in four partially interconnected signaling pathways that control angiogenesis and endothelial permeability. Cerebral cavernous malformations can occur sporadically, or as a familial autosomal dominant disorder (FCCM) with incomplete clinical and neuroradiological penetrance and great inter-individual variability. Although the clinical course is unpredictable, symptoms typically present during adult life and include headaches, focal neurological deficits, seizures, and potentially fatal stroke. In addition to neural lesions, extraneural cavernous malformations have been described in familial disease in several tissues, in particular the skin. We here present seven novel FCCM families with neurologic and cutaneous lesions. We review histopathological and clinical features and provide an update on the pathophysiology of cerebral cavernous malformations and associated cutaneous vascular lesions. (c) 2016 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)338-351
Number of pages14
JournalAmerican Journal of Medical Genetics Part A
VolumePart A 173A
Issue number2
DOIs
Publication statusPublished - Feb 2017

Keywords

  • cerebral cavernous malformation
  • CCM
  • cutaneous cavernous malformation
  • DOMAIN-ASSOCIATED PROTEIN-1
  • CUTANEOUS VENOUS MALFORMATIONS
  • NATURAL-HISTORY
  • ENDOTHELIAL-CELLS
  • RECENT INSIGHTS
  • VASCULAR MALFORMATIONS
  • CCM PATHOGENESIS
  • BINDING-PROTEIN
  • 2-HIT MECHANISM
  • MOUSE MODEL

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