NF1-vasculopathy includes stenosis, aneurysms and arteriovenous malformations occurring in patients with NF1 [3, 5]. It is an underestimated complication because a diagnosis is usually made only in patients with specific clinical manifestations. The prevalence of vascular lesions in NF1 ranges from 0,4% to 6,4% of all patients [6]. The most common site of involvement is renal artery, which tends to be more frequently stenotic than aneurysmal [7]; in Oderich et al. [3], 76 vascular abnormalities were diagnosed in 31 patients (mean age 38 ± 16 years): only 4% was RAA, while renal artery stenosis accounted for about 12% of all the vascular abnormalities. Other vessels could be affected, such as cerebral, carotid and aortic arteries. Most patients with NF1 vascular abnormalities are asymptomatic. When the renal arteries are involved, hypertension is the most frequent presentation [3]. Both renal artery stenosis and aneurysm can cause renovascular hypertension [8,9,10]; the pathogenesis of hypertension in renal artery stenosis is well-known (linked to activation of renin-angiotensin-aldosterone system), while the association between RAA and hypertension is not clearly understood, probably related to altered renal flow from kinking or torsion that causes decreased kidney perfusion [11, 12]. Several pathogenetic hypotheses about NF1 vasculopathy were postulated [13]. Some authors suggested that intimal thickening in NF1 vasculopathy is the result of proliferation of Schawann cells within the artery or it depends on compression or invasion by neural tumors. Another theory is related to neurofibromin deficiency; it has been demonstrated by immunohistochemistry that neurofibromin is expressed by endothelial and smooth muscle cells [14] and its deficiency may cause proliferation within vessel wall, a process analogous to that which produces cutaneous neurofibromas [3]. A genotype-phenotype correlation, between a specific pathogenic variant in NF1 gene and vasculopathy, has not yet been found [15]. To our best knowledge, there is no other case of RAA in a child with NF1 reported in current literature. A few cases of RAA in adults NF1 patients have been described, often complicated by hypertension [8,9,10]; spontaneous rupture without risk factors may occur, with four cases reported [16,17,18,19].
For the diagnosis of renal artery abnormalities in patients with NF1, the first-line imaging technique is color-doppler ultrasonography. This procedure is non-invasive and commonly accepted by pediatric patients; it could be used as an instrument of screening in asymptomatic NF1 patients and a follow-up tool in children with any known renal abnormalities. The limitation of color-doppler ultrasonography includes poor cooperation and difficulty in visualizing the entire renal artery due to overlying bowel gas [20]. Other diagnostic modalities are computed tomography, magnetic resonance imaging, and arteriography. In our asymptomatic case, renal color-doppler ultrasound, performed as a screening tool in a patient with NF1, was very useful in the diagnosis of RAA.
As regards treatment, it depends on the type of renal abnormality and the associated symptoms. Firstly, children with hypertension can be managed conservatively through medical therapy; if blood pressure is poorly controlled with anti-hypertensive drugs, surgical intervention is warranted [21]. In the case of RAA, the indications for endovascular treatment (stent-grafting or coil embolization) are size > 2 cm, female gender within childbearing age, symptoms like pain, hematuria, medically refractory hypertension including that associated with functionally important renal artery stenosis, thromboembolism, dissection and rupture [22]. In our case, coil embolization is required because of the presence of a dissecting aneurysm, with an elevated risk of spontaneous rupture. The complications of endovascular procedures include renal infarction, pain, hypertension, and fever. As observed in our case, hypertension occurs after coil embolization, most likely secondary to partial renal infarction. A close surveillance of blood pressure in these patients is needed in order to reveal either the onset of hypertension or the worsening of preexisting hypertension [23].
In conclusion, vasculopathy is a well-known complication in NF1 patients. The finding of a vascular abnormality in a specific site requires the evaluation of the entire vascular system because multiple vessels could be involved at the same time. In our opinion, this case is relevant because among the vascular abnormalities in NF1, RAA is a rare manifestation, with only a few cases regarding adult patients and no pediatric reports described in current literature. Our child was asymptomatic at the diagnosis and the identification of this life-threatening condition was possible thanks to the early starting of the screening program for major NF1 complications. We suggest monitoring the blood pressure of all patients that undergo coil embolization for RAA to facilitate early recognition of hypertension.
