Abstract Details

To describe a case of multiple cavernous malformations secondary to a PDCD10 gene mutation.

Cerebral cavernous malformations (CCMs) are vascular abnormalities with densely packed dilated vessel cavities with a single layer of endothelium and no intervening brain parenchyma. They can be asymptomatic or manifest clinically: headaches, focal neurologic deficits, stroke, and seizures. The prevalence of CCMs is reported as 0.1 to 0.5%. The Programmed Cell Death 10 (PDCD10) gene, on chromosome 3q, is implicated in their formation and accounts for 10-15% of genetic CCMs. 

There are three genes currently discovered to be implicated in CCMs: KRIT1/CCM1, MGC4607/CCM2, PDCD10/CCM3. These three are seen in both sporadic and familial CCM, more commonly in the familial form, which has autosomal dominant inheritance, incomplete penetrance, and variable expressivity. It is associated with multiple brain lesions and an earlier clinical presentation. The sporadic form is associated with an isolated lesion and later clinical presentation. PDCD10/CCM3 mutations are specifically associated with a more severe form of CCM, often manifesting younger with higher risk of hemorrhage. Other disease manifestations exist such as cutaneous vascular malformations, scoliosis, spinal cord cavernomas and meningiomas.

58 year old female who presented to outpatient neurology with concerns of worsening gait disturbance, falls, and cognitive issues. She had no other symptoms. Neuropsychologic evaluation showed no evidence of neurodegenerative process. The patient’s sister died of ICH secondary to a CCM.

CCMs are present in a small percentage of the population, 0.1-0.5%, as stated above and of that, only 10-15% are caused by the PDCD10 mutation, which is also a more severe form. Genetic testing for this mutation provides for the opportunity for continued study for possible treatments and future management.