Therefore, it comes of no surprise that disturbances of collagen expression is related to severe disorders, such as HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps) syndrome, a COL4A1-related disorder that presents with retinal tortuosity and muscle cramps and with variable combinations of small vessel brain disease [56], or the “COL4A1 stroke syndrome” [81]. Here, COL4A1 is linked to stroke disorder.