moyamoya disease

A founder variant of RNF213, p.R4810K (c.14429G>A, rs112735431), was recently identified as a major genetic risk factor for moyamoya disease (MMD) in Japan. Although the association of p.R4810K was reported to be highly significant and reproducible, the disease susceptibility of other RNF213 variants remains largely unknown. In the present study, we systematically evaluated the coding variants detected in Japanese patients and controls for associations with MMD. To detect variants of RNF213, all coding exons were sequenced in 27 Japanese MMD patients without p.R4810K. We also validated all previously reported variants in our case-control samples and tested for associations in combination with previous Japanese study cohorts, including the 1000 Genomes Project data set, as population-based controls. Forty-six missense variants other than p.R4810K were identified among 370 combined patients and 279 combined controls in Japan. Sixteen of 46 variants were polymorphisms with minor all...

To study the risk factors for the development of moyamoya syndrome after cranial irradiation for primary brain tumors in children. We reviewed neuroimaging studies and dosimetry data for 456 children who were treated with radiation for a primary brain tumor and who were prospectively evaluated with serial neuroimaging studies and neurologic evaluations. A total of 345 patients had both adequate neuroimaging and radiation dosimetry data for further analysis. We used survival analysis techniques to examine the relationship of clinically important variables as risk factors for the development of moyamoya over time. Overall, 12 patients (3.5%) developed evidence of moyamoya. The onset of moyamoya was more rapid for patients with neurofibromatosis type 1 (NF1) (median of 38 vs 55 months) and for patients who received >5,000 cGy of radiation (median of 42 vs 67 months). In a multiple Cox proportional hazards regression analysis controlling for age at start of radiation, each 100-cGy increase in radiation dose increased the rate of moyamoya by 7% (hazard ratio [HR] = 1.07, 95% CI: 1.02 to 1.13, p = 0.01) and the presence of NF1 increased the rate of moyamoya threefold (HR = 3.07, 95% CI: 0.90 to 10.46, p = 0.07). Moyamoya syndrome is a potentially serious complication of cranial irradiation in children, particularly for those patients with tumors in close proximity to the circle of Willis, such as optic pathway glioma. Patients who received higher doses of radiation to the circle of Willis and with neurofibromatosis type 1 have increased risk of the development of moyamoya syndrome.

Chronic ischemia in adult moyamoya disease (MMD) reduces the integrity of normal-appearing white matter (WM). We investigated whether covert WM impairment alters large-scale brain networks as well as specific neural circuits associated with neurocognitive dysfunction in MMD. A total of 46 participants (control, n = 23; MMD, n = 23) were examined using diffusion tensor imaging and streamline tractography. Structural connectivity among 90 cortical and subcortical brain regions was evaluated using the mean fractional anisotropy along the fiber tracts. Graph theoretical analysis was used to measure network parameters and inter-regional connectivity. Global network parameters were reduced in patients with MMD, including cluster coefficient (controls vs. MMD: 3.62 ± 0.24 vs. 3.26 ± 0.36; p < 0.0001), characteristic path length (controls vs. MMD: 1.20 ± 0.02 vs. 1.17 ± 0.01; p < 0.001), and small-world property (controls vs MMD: 3.07 ± 0.18 vs. 2.83 ± 0.27; p < 0.001). Reduced pai...