Moyamoya disease-5 (MYMY5; 614042) is caused by mutation in the ACTA2 gene (102620) on the long arm of chromosome 10 (10q23.3); and moyamoya disease-6 with achalasia (MYMY6; 615750) is caused by mutation in the GUCY1A3 gene (139396) on the long arm of chromosome 4 (4q32). Loci for the disorder have been mapped to the short arm of chromosome 3 (MYMY1) and the long arm of chromosome 8 (8q23) (MYMY3; 608796). See also MYMY4 (300845), an X-linked recessive syndromic disorder characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism, and linked to q25.3, on chromosome 17.In Japan the overall incidence is higher (0.35 per 100,000). In North America, women in the third or fourth decade of life are most often affected, but the condition may also occur during infancy or childhood. These women frequently experience transient ischaemic attacks (TIA), cerebral hemorrhage, or may not experience any symptoms at all. They have a higher risk of recurrent stroke and may be experiencing a distinct underlying pathophysiology compared to patients from Japan.Moyamoya disease can be either congenital or acquired. Patients with Down syndrome, sickle cell anemia, neurofibromatosis type 1, congenital heart disease, fibromuscular dysplasia, activated protein C resistance, or head trauma can develop moyamoya malformations. It is more common in women than in men, although about a third of those affected are male. Pathophysiology
The disease moyamoya, which is a Japanese mimetic word, gets its characteristic name due to the appearance of smoke on relevant angiographs resultant from the tangle of tiny vessels in response to stenosis.
There is also evidence that identifies hyperthyroidism and congenital dwarfing syndromes as two of the more loosely associated syndromes that correlate with the possibility of being diagnosed with moyamoya disease later in life.There is also research that has shown that certain radiographic biomarkers that lead to the diagnosis of moyamoya disease have been identified. The specific radiographic markers are now considered an acceptable key component to moyamoya disease and have been added to the International Classification of Diseases (ICD). These biomarkers of moyamoya are "stenosis of the distal ICAs up to and including the bifurcation, along with segments of the proximal ACA and MCA...dilated basal collateral vessels must be present"  Some other common findings that have not been added to the classification index of those with moyamoya disease which are found using radiography involve very distinct changes in the vessels of the brain. These changes include newly formed vessels made to compensate for another change noted, ischemia and cerebrovascular reserve, both found on MRI. Functional changes include evidence of ischemia in vessels of the brain (ICA, ACA, MCA, specifically). It is important to also note that the radiographic biomarkers, in order to be classified as moyamoya disease, all findings must be bilateral. If this is not the case and the findings are unilateral, it is diagnosed as moyamoya syndrome.There are also several protein biomarkers that have been linked to the moyamoya disease diagnosis.