Familial Cerebral Cavernous Malformation: Investigation Strategy and Treatment Options
2Department of Medical Imaging, Baruch Padeh Medical Center, Israel, Israel
3Institute of Human Genetics, Galilee Medical Center, Israel, Israel
Purpose: The main aim of our article is to document an uncommon pathology (to the best of our knowledge there is only one reported case of FCCM in Jewish population) as well as to review the literature of management.
Methods: We present two siblings who have gone MRI scans at our institution: one for follow up of cerebral cavernous hemangiomas after major brain bleeding; another one sent for an MRI scan due to headaches and a picture of the FCCM was a coincidental finding.We have collected clinical and radiological information, familial screening(by questioning the mother of the patients), and management decisions about our patients.
Our patients have undergone genetic counseling and DNA- next generation sequencing (NGS) of four known causative genes for FCCM; KRIT1, CCM2, PDCD10 and PIK3CA.
Results: The MRI study has shown classic pattern of FCCM.
The genetic counseling with gene sequencing has shown a novel heterozygous pathogenic genetic variant c.404_405insCAGC (insertion type), in PDCD10–also known as CCM3, this was confirmed by Sanger sequencing.
CCM3 has a more aggressive course than CCM1 and CCM2 [2] and may present at younger age and more frequent intracerebral hemorrhages. CCM4 was reported to be sporadic and not familial.
Conclusions: After extended literature review, we found no sharp and uniform consensus of management strategies due to lack of clinical trials probably due to the rarity of the disease. Although there are some recommendations of management there is still space for case-by-case decisions. It`s advised to take the decisions in a multidisciplinary setting including neurologist, neurosurgeon, radiologist and geneticist.
Genetic consultation and testing have a crucial role, in discovering pre-symptomatic cases in the extended family to be followed carefully and treated before a catastrophic even occurs, as well as and in family planning.