Molecular diagnosis in cerebral cavernous malformations

Neurologia. 2017 Oct;32(8):540-545. doi: 10.1016/j.nrl.2015.07.001. Epub 2015 Aug 21.
[Article in English, Spanish]


Introduction: Cerebral cavernous malformations (CCMs; OMIM 116860) are enlarged vascular cavities without intervening brain parenchyma whose estimated prevalence in the general population is between 0.1% and 0.5%. Familial CCM is an autosomal dominant disease with incomplete clinical and radiological penetrance. Three genes have been linked to development of the lesions: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10.

Development: The aetiological mutation is not detected in a large percentage of cases and new approaches are therefore needed. The aim of this review is to analyse current molecular techniques and the possible mutations or variations which can be detected in a molecular genetics or molecular biology laboratory. Likewise, we will analyse other alternatives that may help detect mutations in those patients showing negative results.

Conclusions: A molecular diagnosis of cerebral cavernous malformations should provide at least the copy number variation and sequencing of CCM genes. In addition, appropriate genetic counselling is a crucial source of information and support for patients and their relatives.

Keywords: CCM1; CCM2; CCM3; Cavernomatosis cerebral; Cerebral cavernous malformations; DNA sequencing; Multiplex ligation-dependent probe analysis; Secuenciación.

Publication types

  • Review

MeSH terms

  • Apoptosis Regulatory Proteins / genetics
  • Carrier Proteins / genetics
  • DNA Copy Number Variations
  • Genetic Testing / methods*
  • Hemangioma, Cavernous, Central Nervous System / diagnosis*
  • Hemangioma, Cavernous, Central Nervous System / genetics*
  • Humans
  • KRIT1 Protein / genetics
  • Membrane Proteins / genetics
  • Mutation / genetics*
  • Proto-Oncogene Proteins / genetics


  • Apoptosis Regulatory Proteins
  • CCM2 protein, human
  • Carrier Proteins
  • KRIT1 Protein
  • KRIT1 protein, human
  • Membrane Proteins
  • PDCD10 protein, human
  • Proto-Oncogene Proteins