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Multiple cerebral cavernous malformations associated with extracranial mesenchymal anomalies

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Abstract

Cerebral cavernous malformations (CCM) are common hamartous dysplasias characterized by abnormally dilated vascular channels. CCM mostly occur sporadically, and multiple occurrence of CCM is highly suggestive of a genetic origin of the disorder. Typical clinical symptoms are seizures, hemorrhages, focal neurological deficits, and headaches. Three genes have so far been described that are responsible for most cases of familial CCM and more than half of the sporadic cases with multiple CCM (CCM1–3). The coincidence of CCM and other vascular anomalies has been described before. The present review discusses the association of CCM with mesenchymal anomalies, with special emphasis on the possible common pathogenetic pathway for CCM and atrial myxomas. An illustrative case is presented in which CCM occurred together with different dysplasias (multiple CCM, liver cavernoma, and cardiac atrial myxoma), which are all thought to arise from abnormal mesenchymal cell differentiation processes.

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Acknowledgements

The authors want to thank Ute Felbor, M.D., Ph.D., from the Institute of Human Genetics, University of Würzburg, for the genetic analysis of the presented case and helpful comments.

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Authors and Affiliations

  1. Department of Neurosurgery, Ludwig-Maximilians-University of Munich, University Hospital, Munich, Germany

    Ardavan Ardeshiri, Ardeshir Ardeshiri & Peter A. Winkler

  2. Department of Cardiac Surgery, Ludwig-Maximilians-University of Munich, University Hospital, Munich, Germany

    Andres Beiras-Fernandez

  3. Institute of Human Genetics, Ludwig-Maximilians-University of Munich, University Hospital, Munich, Germany

    Ortrud K. Steinlein

  4. Laboratory for Nerosurgival Microanatomy, Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany

    Peter A. Winkler

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  1. Ardavan Ardeshiri
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  2. Ardeshir Ardeshiri
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Correspondence to Peter A. Winkler.

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Comments

Ulrich Sure, Marburg, Germany

Ardeshiri et al. present a unique case of cerebral cavernoma associated with a cardial myxoma. The paper represents a well-written case report in which possible genetic alterations within the CCM1–3 genes were also extensively studied. The authors nicely review the current literature on extracranial mesenchymal anomalies associated with cerebral cavernomas that have been reported so far. This data is nicely summarized in Table 1 and shows that extracranial vascular malformations associated with cavernomas seem to be more likely than nonvascular extracranial lesions. Since the time that I was aware of possible cutaneous manifestation in CCM disease, I discovered three individuals with such a phenotype in our institution. All these were patients suffering from multiple cavernomas. Therefore, these were more likely to bear a CCM-related genetic alteration and are currently studied for mutations. The present case also harbored multiple lesions but unfortunately was not successfully diagnosed for a specific CCM mutation.

In summary, I think this is an important paper because (1) it shows that we should look at associated mesenchymal pathologies in patients with multiple cavernomas and (2) we should offer genetic testing to these individuals to inform our patients about their possible risk to pass on the same disease to the next generation, more likely even at a younger age (1).

Reference

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Ardeshiri, A., Ardeshiri, A., Beiras-Fernandez, A. et al. Multiple cerebral cavernous malformations associated with extracranial mesenchymal anomalies. Neurosurg Rev 31, 11–18 (2008). https://doi.org/10.1007/s10143-007-0111-7

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