Meng Luen LEE, Tung Ming CHANG, Rei Cheng YANG, Albert D. YANG, Ming CHEN

Systemic hypertension followed by insidious stroke in a 12-year-old boy with childhood neurofibromatosis type 1 presenting with renal and cerebral artery vasculopathy

Neurofibromatosis type 1 (NF1)-associated vasculopathy is usually diagnoseddecades after the clinical diagnosis of NF1. Childhood NF1-associated renalartery vasculopathy or moyamoya-like brain vasculopathy could be clinicallysilent for a long time. We report a 12-year-old boy who had systemic hypertensionfound incidentally at a routine check-up. Physical examination showed caféau-lait spots and strong radial pulses. Abdominal computerized tomographyangiography showed severe right ostial renal artery stenosis. Genomic studyshowed a heterozygous mutation c.5902C>T (p.R1968*) and two heterozygoussingle nucleotide polymorphisms (NCBI: SNP rs18011052 and rs2905876) ofNF1 gene. After endovascular revascularization for renovascular hypertensioncaused by renal artery stenosis, including percutaneous transluminal renalangioplasty and stent implantation, blood pressure dropped effectively from205/143 mmHg to 130/90 mmHg. Supine renin level dropped from 87.2 pg/mL to 47.9 pg/mL. Unfortunately, right hemiplegia, transient visual loss withblind spots (scotomas), and clumsiness of extremities emerged insidiously3.5 months later. Brain magnetic resonance imaging and magnetic resonanceangiography showed ischemic infarction involving the watershed area of theanterior and middle cerebral arteries, indicating presence of moyamoya-likebrain vasculopathy. A dilemma is that a significant decrease of blood pressureafter endovascular revascularization for renal artery stenosis may havepotentially unmask the moyamoya-like brain vasculopathy in this patient.Vasculopathy could be heralding childhood NF1 in the young patients withoutfull-fledged clinical features. Endovascular revascularization for renal arterystenosis could be a double-edge sword in childhood NF1 presenting withconcomitant renal and cerebral artery vasculopathy.

PDF

___

1. Sabbagh A, Pasmant E, Imbard A, et al. NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: The French experience. Hum Mutat 2013; 34: 1510-1518.

2. DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 2000; 105(3 Pt 1): 608-614.

3. Hamilton SJ, Friedman JM. Insights into the pathogenesis of neurofibromatosis 1 vasculopathy. Clin Genet 2000; 58: 341-344.

4. Rosser TL, Vezina G, Packer RJ. Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1. Neurology 2005; 64: 553- 555.

5. Ghosh PS, Rothner AD, Emch TM, Friedman NR, Moodley M. Cerebral vasculopathy in children with neurofibromatosis type 1. J Child Neurol 2013; 28: 95-101.

6. Cairns AG, North KN. Cerebrovascular dysplasia in neurofibromatosis type 1. J Neurol Neurosurg Psychiatry 2008; 79: 1165-1170.

7. Rea D, Brandsema JF, Armstrong D, et al. Cerebral arteriopathy in children with neurofibromatosis type 1. Pediatrics 2009; 124: e476-e483.

8. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis type 1 revisited. Pediatrics 2009; 123: 124-133.

9. Oderich GS, Sullivan TM, Bower TC, et al. Vascular abnormalities in patients with neurofibromatosis syndrome type I: Clinical spectrum, management, and results. J Vasc Surg 2007; 46: 475-484.

10. Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: An analysis using U.S. death certificates. Am J Hum Genet 2001; 68: 1110-1118.

11. Bajaj A, Li QF, Zheng Q, Pumiglia K. Loss of NF1 expression in human endothelial cells promotes autonomous proliferation and altered vascular morphogenesis. PLoS One 2012; 7: e49222.

12. Srinivasan A, Krishnamurthy G, Fontalvo-Herazo L, et al. Angioplasty for renal artery stenosis in pediatric patients: An 11-year retrospective experience. J Vasc Interv Radiol 2010; 21: 1672-1680.

13. Tyagi S, Kaul UA, Arora R. Endovascular stenting for unsuccessful angioplasty of the aorta in aortoarteritis. Cardiovasc Intervent Radiol 1999; 22: 452-456.

14. Koss M, Scott RM, Irons MB, Smith ER, Ullrich NJ. Moyamoya syndrome associated with neurofibromatosis Type 1: Perioperative and longterm outcome after surgical revascularization. J Neurosurg Pediatr 2013; 11: 417-425.

15. Hayashi T, Shirane R, Fujimura M, Tominaga T. Postoperative neurological deterioration in pediatric moyamoya disease: Watershed shift and hyperperfusion. J Neurosurg Pediatr 2010; 6: 73-81.