ORPHA: 2573; DO: 13099;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q23.31 | Moyamoya disease 5 | 614042 | 3 | ACTA2 | 102620 |
A number sign (#) is used with this entry because of evidence that moyamoya disease-5 (MYMY5) is caused by heterozygous mutation in the ACTA2 gene (102620) on chromosome 10q23.
See also familial thoracic aortic aneurysm-6 (AAT6; 611788) and multisystemic smooth muscle dysfunction syndrome (MSMDS; 613834), which can also be caused by mutation in the ACTA2 gene.
Moyamoya disease is a cerebrovascular disorder caused by stenotic changes of terminal portions of the internal carotid arteries accompanied by surrounding fine arterial collateral vessels. These vascular networks resemble a 'puff of smoke' (Japanese: moyamoya) in angiographic imaging (summary by Roder et al., 2011).
For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350).
Guo et al. (2009) reported 3 unrelated families segregating both thoracic aneurysms with dissection (TAAD) and moyamoya disease. Onset of stroke in these families ranged from 5 to 46 years. Some patients had isolated moyamoya, some had isolated thoracic aneurysm, and some had both conditions.
The transmission pattern of moyamoya disease in the families reported by Guo et al. (2009) was consistent with autosomal dominant inheritance.
In affected members of 3 unrelated families with moyamoya disease, Guo et al. (2009) identified 3 different heterozygous mutations in the ACTA2 gene (see, e.g., R258H, 102620.0002 and R258C, 102620.0003). Several members of all families also had TAAD, but isolated moyamoya disease was found in 1 member of each family.
Roder et al. (2011) identified a heterozygous mutation in the ACTA2 gene (R179H; 102620.0004) in 1 of 39 unrelated patients of European descent with moyamoya disease and no family history of the disorder. The patient had onset of stroke at age 3 years. No other previously described ACTA2 mutations associated with moyamoya disease (Guo et al., 2009) were found in this cohort.
Guo, D.-C., Papke, C. L., Tran-Fadulu, V., Regalado, E. S., Avidan, N., Johnson, R. J., Kim, D. H., Pannu, H., Willing, M. C., Sparks, E., Pyeritz, R. E., Singh, M. N., and 19 others. Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and moyamoya disease, along with thoracic aortic disease. Am. J. Hum. Genet. 84: 617-627, 2009. [PubMed: 19409525] [Full Text: https://doi.org/10.1016/j.ajhg.2009.04.007]
Roder, C., Peters, V., Kasuya, H., Nishizawa, T., Wakita, S., Berg, D., Schulte, C., Khan, N., Tatagiba, M., Krischek, B. Analysis of ACTA2 in European moyamoya disease patients. Europ. J. Paediat. Neurol. 15: 117-122, 2011. [PubMed: 20970362] [Full Text: https://doi.org/10.1016/j.ejpn.2010.09.002]