Original research articleCircle of Willis abnormalities in children with neurofibromatosis type 1
Introduction
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition caused by a mutation in, or a deletion of, the NF1 gene located within the long arm of chromosome 17. More than 250 mutations have been identified in affected individuals. The gene product – neurofibromin – serves as a tumor suppressor. The estimated incidence of NF1 is 1:3000 [1].
Clinical diagnosis of NF1 is established in the presence of at least 2 of 7 criteria: (1) six or more café-au-lait spots or hyperpigmented macules greater than or equal to 5 mm in diameter in children younger than 10 years and to 15 mm in adults, (2) axillary or inguinal freckles, (3) two or more typical neurofibromas or one plexiform neurofibroma, (4) optic nerve glioma, (5) two or more iris hamartomas (Lisch nodules), (6) sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis, (7) first-degree relative with NF1 [2].
Renal artery stenosis secondary to fibromuscular dysplasia and other vascular lesions, also in the central nervous system (CNS), such as vascular ectasias, stenoses, moyamoya disease, and aneurysms, are reported more frequently in patients with NF1 than in general population [3], [4]. Rarely, coronary artery aneurysms are identified in symptomatic or even asymptomatic individuals with NF1 [5].
Available literature contains mainly case reports concerning CNS vasculopathy. To our knowledge, there are only three papers based on the bigger material [6], [7], [8]. The purpose of this study is to assess the presence of anatomical variants and vascular abnormalities in cerebral arteries in children with NF1 on magnetic resonance angiography (MRA) in a group of 67 children with NF1.
Section snippets
Materials and methods
The material consisted of 67 children with NF1 diagnosed according to the above mentioned National Institute of Health Criteria Consensus Conference, aged between 9 months and 18 years (mean age 6.6 years). There were 35 boys and 32 girls in this group.
The control group consisted of 90 children aged 2–18 years, mean age 11.8 years (53 girls, 37 boys). The children included in the control group had no signs of CNS injury and were referred to magnetic resonance imaging (MRI) only because of
Results
Cerebral arteriopathy was defined as any abnormality of the intracranial arterial system that could not be considered as normal variant [7]. In the study group, one child (1.5% with 95% confidence interval [0.07%, 9.13%]) showed the signs of cerebral arteriopathy and was diagnosed as moyamoya disease (Fig. 1). We found no aneurysms in the study group and control group.
Twenty-nine children with NF1 (43.3%), 16 boys and 13 girls, turned to have arterial anatomical variants of the circle of Willis
Discussion
The previous, few publications concerning cerebrovascular anomalies in children with NF1 are not comparable with our study. In the first of them, by Rosser et al. [6], brain MR examinations of 316 children were retrospectively reviewed. Eight of these patients had brain abnormalities indicating vascular pathology and these 8 patients only underwent MRA. Seven of them showed signs of cerebral arteriopathy as defined above; in the eighth patient an anatomical variant was found (hypoplastic right
Conclusions
- 1.
The occurrence of arterial anatomical variants in NF1 patients was twofold higher than in general population which was statistically significant.
- 2.
In the study group multiple anatomical variants were more frequent than in the control group although the difference did not reach statistical significance.
- 3.
The prevalence of cerebral arteriopathy in children with NF1 was 1.5% in our material which is rarer than estimated in other, few papers.
Conflict of interest
None declared.
Acknowledgement and financial support
None declared.
Ethics
The work described in this article has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans; Uniform Requirements for manuscripts submitted to Biomedical journals.
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