A Case of Multiple Intracranial Major Artery Stenoses With Coexisting p.E32K and p.R4810K Variants.

OBJECTIVES

Familial hypercholesterolemia (FH), caused by p.E32K, is characterized by early-onset coronary artery disease. However, the relationship between p.E32K and cerebrovascular disease is unclear. One of our patients with the p.E32K had several intracranial artery stenoses (ICAS). The objective of this case series was to identify factors that may be associated with ICAS in the variant carriers.

METHODS

A 75-year-old Japanese woman with FH carrying p.E32K was found to have 5 asymptomatic ICAS when brain magnetic resonance angiography (MRA) was performed. We retrospectively investigated additional patients with FH who underwent brain MRA at our institution to explore the unknown factors accelerating ICAS.

RESULTS

We investigated an additional 5 patients with FH who underwent brain MRA. Of them, only one had mild ICAS. The p.R4810K that is an established genetic risk for ICAS, particularly in East Asians, was identified only in the patient with 5 ICAS.

DISCUSSION

PCSK9 and RNF213 play an important role in lipid metabolism and endothelial integrity. Therefore, together, these variants could be involved in the development of multiple ICAS. Our case series indicated that p.E32K carriers should undergo early brain screening to obtain appropriate stroke prevention measures in the asymptomatic stage.