gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

Genetics of cerebral cavernomas

Genetik zerebraler Kavernome

Meeting Abstract

  • corresponding author U. Sure - Neurochirurgische Klinik, Klinikum der Philipps-Universität, Marburg
  • O. Sürücü - Neurochirurgische Klinik, Klinikum der Philipps-Universität, Marburg
  • H. Bertalanffy - Neurochirurgische Klinik, Klinikum der Philipps-Universität, Marburg
  • U. Felbor - Institut für Humangenetik, Universität Würzburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocSA.11.01

The electronic version of this article is the complete one and can be found online at:

Published: May 8, 2006

© 2006 Sure et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Cerebral cavernous malformations (CCM) are biologically active vascular abnormalities that occur with a frequency of 0.1% to 0.5% in the general population and cause recurrent headaches, seizures and focal neurological deficits. There are sporadic forms of CCM with autosomal dominance. It is Important to note that seemingly sporadic cases with multiple lesions are generally hereditary. Causal mutations have been demonstrated in three genes, KRIT1, MGC4607, and PDCD10 (CCM 1-3).

Methods: Over the past five months, four families with a familial CCM syndrome and three sporadic patients with multiple lesions were admitted to our neurosurgical department. The family histories were summarized in pedigrees. Genomic DNA of clinically affected and non-affected family members is currently analyzed. Coding CCM1, CCM2, and CCM3 exons with their adjacent splice sites are PCR-amplified, sequenced, and, when necessary subcloned.

Results: So far, we have analyzed one seemingly sporadic patient with multiple lesions and one familial case. Two novel CCM1 frameshift mutations were identified. A three year-old Bosnian girl with a large symptomatic brainstem cavernoma and multiple supratentorial cavernomas carried a one base pair insertion in CCM1 exon 16 (g.1683_1684insA; p.V562fsX567). MR imaging of her asymptomatic parents revealed multiple lesions in her mother. Genetic analyses confirmed the mutation in the mother, but not the father. A mutation in exon 17 of CCM1 was found in a known German CCM family (IFCAS-102). In addition to a four base pair deletion, patients of this family carry the largest thus far published CCM1 insertion: g.1780-1783delinsTACCTGTTACCAAA. This frameshift mutation results in a premature stop codon at position 607 (p.A594fsX607).

Conclusions: Our results demonstrate that genetic counseling and testing is indicated for patients with a positive family history and for seemingly sporadic cases with multiple lesions. The identification of a mutation enables precise genetic testing for relatives. Given the 50% a priori risk of autosomal dominant inheritance, the benefits of genetic testing are twofold: a positive test result in a presymptomatic carrier permits close neuroradiological surveillance and timely neurosurgical intervention; a negative test result relieves the patient of unwarranted anxiety and unnecessary medical supervision.