NF1 (OMIM #162200) is an autosomal dominant multisystem genetic disorder caused by a mutation in the NF1 gene on chromosome 17 (17q11.2). The clinical diagnostic criteria for NF1 were established in 1988 by the National Institute of Health and are satisfied when two of the following symptoms are met [5
]: café-au-lait spots on the skin (≥6 spots >5
mm before puberty or >15
mm after puberty), intertriginous freckling (axillae, groin, and neck), dermal neurofibroma (≥2), optic pathway glioma, iris hamartoma (Lisch nodules), skeletal dysplasia (tibial dysplasia or sphenoid wing dysplasia), and a positive family history of NF1 affecting a first-degree relative. Café-au-lait spots, which are present in all patients, may be the only feature apparent in some patients, especially infants and children. Young children with multiple café-au-lait spots and no other NF1 features whose parents do not show signs of NF1 are recommended to undergo ophthalmologic examination. Lisch nodules are not considered an ophthalmologic complication, while multiple Lisch nodules, unlike café-au-lait spots and neurofibromas, are specific to neurofibromatosis [5
]. Moreover, symptomatic optic pathway glioma in individuals with NF1 usually presents before 8 years of age with loss of visual acuity or proptosis, but these tumors may not become symptomatic until later in childhood or even adulthood.
NF1 is associated with vasculopathy, which is a significant but underrecognized complication that affects multiple sites, including thoracic, abdominal, renal, and intracranial vessels. Vasculopathy may lead to occlusions and aneurysms of any known size at any location in the body, and when involving major arteries or arteries of the heart or brain, vasculopathy can have serious or even fatal consequences [6
]. NF1 vasculopathy can produce renal artery stenosis, coarctation of the aorta, and other vascular lesions associated with hypertension. Renal artery stenosis has been recognized as the most common form of secondary hypertension in children with neurofibromatosis. However, there are only a few reports of thoracic aortic coarctation in association with hypertension and neurofibromatosis [4
]. It is noteworthy that not all NF1 vasculopathy is congenital, but at least some NF1 vasculopathy progresses after birth [8
]. Similar to the findings presented in previous reports [7
], the gross and microscopic pathologic findings in our patient reflected the aortic coarctations found in patients with neurofibromatosis, including intimal hyperplasia of proliferating smooth muscle cells and luminal narrowing ().
Neurofibromin, the protein product of NF1, is normally expressed in the epithelial and smooth muscle cells of blood vessels, can regulate cell growth through Ras regulation, and is less likely to be involved in pathogenesis, but its precise mechanisms are poorly understood [10
]. It has been reported in animal models [11
] and in studies of human endothelial cells [12
] that the loss of neurofibromin expression in endothelial cells may cause proliferation of vascular smooth muscle cells.
In summary, a 4-year-old girl underwent successful cardiac surgery for hypoplasia of the thoracic aorta after presenting with NF1 and severe hypertension. Taken together, ophthalmologic examination is recommended for young children with multiple café-au-lait spots. Furthermore, it is important to note that appropriate cardiac examination and blood pressure monitoring should be part of the routine care provided to NF1 patients.