Moyamoya syndrome in children with neurofibromatosis type 1: Italian–French experience

Abstract

Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered. This study included 18 children. The mean age was 2.93 ± 3.03 years at the NF1 diagnosis and 7.43 ± 4.27 years at the MMS diagnosis. In seven patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was performed in 10 patients due to clinical symptoms, including headache (n = 6), cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining eight children (47%) had MMS diagnosed incidentally. Sixteen children were characterized molecularly. The features of MMS were similar between patients with and without NF1. Additionally, the NF1 phenotype and genotype were similar between children with and without MMS. Interestingly, three children experienced tumors with malignant histology or behavior. The presence of two first cousins in our cohort suggested that there may be potential genetic factors, not linked to NF1, with an additional role respect of NF1 might play a role in MMS pathogenesis. The incidental diagnosis of MMS, and the observation that, among children with NF1, those with MMS were clinically indistinguishable from those without MMS, suggested that it might be worthwhile to add an angiographic sequence to brain MRIs requested for children with NF1. A MMS diagnosis may assist in properly addressing an NF1 diagnosis in very young children who do not fulfill diagnostic criteria.

Seizures in children with neurofibromatosis type 1: is neurofibromatosis type 1 enough?

“…The authors have already described three children: patient 10 [ 26 ] patient 11 [ 27 ] and patient 16 [ 28 ], respectively in paper focused on association of NF1 with MMS, hydrocephalus and a benign phenotype associated to Arg1809 substitution.…”

“…Patient 16 had an Arg1809 substitution that was described recently by our group as being related to a mild NF1 phenotype [ 26 ]. Arg1809 substitution is not known to be associated with seizures.…”

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.…”

Association between neurofibromatosis type 1 and cerebrovascular diseases in children: a systematic review

“…The latter, in turn, is characterized by progressive stenosis or occlusion of the internal carotid artery and its branches. For this reason, although lack of full knowledge regarding the natural history, symptoms, etiology and management of such syndrome, it is already known that routine vascular screening/assessment in NF-1 patients is necessary for early identification of this condition [12]. Using such approach, CVD in patients with NF-1 can be diagnosed since childhood.…”