Complex Chromosome Rearrangement of 6p25.3->p23 and 12q24.32->qter in a Child With Moyamoya

Abstract

KEY WORDS moyamoya, 6p trisomy, 12q deletion ABBREVIATIONS ACA-anterior cerebral artery FISH-fluorescence in situ hybridization HLA-human leukocyte antigen ICA-internal carotid artery MCA-middle cerebral artery OMIM-Online Mendelian Inheritance in Man SNP-single nucleotide polymorphism Dr Rosenberg guided conception and oversight of manuscript development and critically reviewed and revised manuscript for intellectual content; Dr Egan collected data, reviewed literature, and drafted the initial manuscript; Dr Rodgers collected and analyzed data; Dr Harter analyzed data and reviewed manuscript for intellectual content; Dr Burnside analyzed data, including statistical analysis, and critically reviewed manuscript for intellectual content; Dr Milla analyzed data; Dr Pappas analyzed data, guided conception and oversight of manuscript development, and critically reviewed manuscript for intellectual content; and all authors approved the final manuscript as submitted. Although pediatric ischemic stroke is an uncommon occurrence, moyamoya is responsible for 6% of cases. [1][2][3] Moyamoya is a cerebrovascular occlusive disorder characterized by bilateral progressive stenosis and occlusion of the distal intracranial internal arteries (ICA) and the proximal anterior and middle cerebral arteries with development of compensatory collateral vessels. The latter appear radiographically as a "puff of smoke" (moyamoya in Japanese). [4][5][6] In juvenile moyamoya, the most common initial presentation is extremity weakness or paralysis secondary to cerebral ischemia. 4,7 Moyamoya was first codified in Japan in 1969. 6 Patients are characterized as having moyamoya syndrome if the vascular findings are associated with an underlying condition, including acquired disorders such as previous cephalic radiation therapy or infection and genetic disorders, such as Down syndrome, neurofibromatosis, sickle cell anemia, and Alagille syndrome. 2,[8][9][10] Moyamoya disease, in contrast, generally refers to idiopathic or isolated, potentially familial, moyamoya.Juvenile moyamoya incidence varies by ethnicity (0.1/100 000 in Caucasian children and 1/100 000 in Japan and Korea) and gender (female: male 2:1) with an overall higher prevalence in families (6%-12%). 10 Genetic influences in moyamoya have been studied in twin, linkage, and identification analyses 11,12 in various ethnic groups, but no consistent finding has emerged. 10,12 This suggests both heterogeneity and epigenetic influences in moyamoya among different ethnic groups, with candidate mutations affecting human leukocyte antigen (HLA)-related genes (6p21), 13 neurofibromatosis-linked genes (17q25), 14 and metalloproteinase inhibitor genes involved in collagen vascular architecture (3p24). 15 Early-onset, or juvenile, and late-onset moyamoya likely have different etiologies, as suggested by HLA-related research in Japan. 16 Within moyamoya-related syndromes, several are also associated with developmental delay. Developmental delay and intellectual disability affects 1% to 3% of US chil...

Foxf2 Is Required for Brain Pericyte Differentiation and Development and Maintenance of the Blood-Brain Barrier

“…Interestingly, several reports have linked white matter abnormalities and stroke to copy-number variations in the relevant chromosomal region, 6p25 (Cellini et al, 2012;Kapoor et al, 2011;Rosenberg et al, 2013;van der Knaap et al, 2006;Vernon et al, 2013). Interpretations are complicated by the fact that FOXC1 are located only 214 kb downstream (centromeric) of FOXF2, and recently genetic variants centromeric of FOXC1 were associated with white matter hyperintensities (French et al, 2014).…”

Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome

“…Risk of MA disease has been also attributed to mutations in GUCY1A3 gene, encoding the major nitric oxide receptor in vascular smooth muscle cells (vSMCs) in achalasia cases [ 11 ]. Other sporadic syndromic cases of MA have been reported, as resumed in Table 1 [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. However, these observations are not able to fully explain the pathogenesis of MA, which is believed to be much more complex.…”

Juvenile Moyamoya and Craniosynostosis in a Child with Deletion 1p32p31: Expanding the Clinical Spectrum of 1p32p31 Deletion Syndrome and a Review of the Literature

“…As MA may be due to the haploinsufficiency of a gene in the 1p32p31 region, and this could be a starting point for future investigations of its genetics aspects, we carefully evaluated all of the genes deleted in our patient. In particular the FOXD3 gene (Forkhead box D3-OMIM 611539) aroused our interest because of its function and its analogy to another FOX gene ( FOXC1 ) that was found to be deleted in another seven-year-old patient with juvenile moyamoya, ID and craniofacial dysmorphisms [ 5 ].…”