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]. The gene discussed is COL4A1; the disease is autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome.