Monogenic diseases, although rare, should be always considered in the diagnostic work up of vascular dementia (VaD), particularly in patients with early onset and a familial history of dementia or cerebrovascular disease. They include, other than CADASIL, Fabry disease, Col4A1-A2 related disorders, which are well recognized causes of VaD, other heritable diseases such as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and cathepsin-A related arteriopathy strokes and leukoencephalopathy (CARASAL). MELAS, caused by mtDNA (80% of adult cases m.3243A>G mutations) and more rarely POLG1 mutations, has minimum prevalence of 3.5/100,000. CARASAL, which is caused by mutations in the CTSA gene, has been described in about 19 patients so far. In both these two disorders cognitive features have not been fully explored and are described only in case series or families. This review paper is aimed at providing an update on the clinical manifestations, with particular focus on cognitive aspects, but also neuroradiological and genetic features of these less frequent monogenic diseases associated with VaD.
Keywords: CARASAL; CARASAL, cathepsin-A related arteriopathy strokes and leukoencephalopathy; COL4A1/A2, gene encoding type IV collagen alpha 1–2 chain; Cerebral small vessel disease; Cognitive impairment; EAN, European academy of neurology; Heritable; MELAS; MELAS, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes; MRI, magnetic resonance imaging; Monogenic diseases; OXPHOS, oxidative phosphorylation system; SLEs, stroke-like episodes; TIA, transitory ischemic attack; VCI, vascular cognitive impairment; VaD, vascular dementia; Vascular dementia; WMHs, white matter hyperintensities; cSVD, cerebral small vessel disease.
© 2022 The Authors. Published by Elsevier B.V.