The Genetic Basis of Moyamoya Disease

Abstract

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a “puff of smoke” (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

Identification of immune-infiltrated hub genes as potential biomarkers of Moyamoya disease by bioinformatics analysis

“…Moyamoya disease (MMD) involves the chronic progressive stenosis of the terminal part of the internal carotid artery and its main branches (middle cerebral artery, and anterior cerebral artery), which becomes an abnormal vascular network with smoke-like (Japanese: Moyamoya) compensatory capillary collaterals as an expression of pathologically increased angiogenic activity at the base of the skull [ 1 , 2 ]. These vascular hallmarks are responsible for the main clinical features of the disease, which are recurrent ischemic and hemorrhagic strokes, often with serious consequences [ 3 ].…”

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

“…Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries (ICA) whose major branches with the emergence of co-existing compensatory abnormal net-like vessels ( 1 – 4 ). MMD is a major cause of stroke in children and young adults and has been observed in different ethnic backgrounds throughout the world, which is reported to be most common in Asian countries such as China, Japan, and Korea ( 5 , 6 ).…”

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

“…MA is frequent in East Asian countries, while rarely reported in Caucasians. The association of MA with genetic disorders, the high familial rate, and the strong linkage with variants of Ring Finger Protein 213 (RNF213)/Mysterin coding gene in East Asian patients strengthen the role of genetic factors in MA pathogenesis [8][9][10][11][12][13][14][15]. Several reports implicated RNF213 as a sensor for mitochondrial dysfunction, hypoxia, and inflammation [14,[16][17][18].…”