Familial multiple cavernous malformations, caused by KRIT-1 mutation

Case contributed by Mustafa Takesh
Diagnosis certain


First episode of witnessed generalized seizure

Patient Data

Age: 50 years
Gender: Male

Numerous heterogeneous, but predominately hyperattenuated lesions of varied shape and size throughout the cerebral hemispheres and to lesser extent in the brainstem and infratentorial compartment.

Selected MRI images demonstrating innumerable punctate to small rounded lesions in both cerebral and cerebellar hemispheres as well as in the brainstem, predominately with classic popcorn appearance and heterogeneous signal on T2w image, while others are better seen on SWI. None of these shows surrounding edema or sign of acute hemorrhage. No mass effect.   

Selected MRI images of the thoracic spine demonstrating a single intramedullary lesion, seen left side at T3/T4 level with popcorn appearance and T2 hypointense rim. 

Case Discussion

This man of Vietnamese origin has a daughter with multiple cavernomas, she was identified to have KRIT-1 gene mutation. He was asymptomatic and found to have the same mutation in KRIT-1 after familial testing. He was investigated with MRI head and spine and found to have multiple cavernomas, including one located intramedullary.

He was given a list of recommendations, such as to avoid hard activities (diving, or mountain climbing) as well as to avoid agents that increase the risk of hemorrhage (aspirin, NSAIDs, heparin and warfarin). In the family history one of his brothers had epilepsy treated with medication since early adulthood. A second bother had chronic headache and vision issues and was diagnosed with multiple cavernomas.

3 years later, the patient presented with the first episode of a witnessed generalized seizure.

The familial cerebral cavernous malformation syndrome (FCCM) is infrequent, but associated with autosomal dominant inheritance. The genetic mutations related to it are KRIT-1 (CCM-1), CCM-2, and PDCD-10 (CCM-3).

There is a wide range of clinical presentations varying from seizures, focal neurological deficits, and cerebral hemorrhage to non-specific headaches. Nevertheless, many cases of FCCM remain asymptomatic.

This case illustrates the importance of identifying familial cerebral cavernous malformation, in order to achieve good outcomes and points out the value of screening of asymptomatic family members with genetic testing.

How to use cases

You can use Radiopaedia cases in a variety of ways to help you learn and teach.

Creating your own cases is easy.