Intima-Type Vasculopathy in Neurofibromatosis Type 1

Introduction: Neurofibromatosis type 1 is an autosomal-recessive, monogenetic disease (NF1 gene 17q22.1) with an incidence of 1:3,000. Clinical symptoms affect skin, eyes, central and peripheral nervous system, and bones. We report about a 10-year-old girl with intima-type vasculopathy followed by peripheral arterial occlusive disease grade 4 according to the neurofibromatosis.

Case Report: At the age of 6 years, a difference in the length of legs was noticed and treated with insoles and orthopedic shoes. At the age of 9 years, consultation of an orthopedic specialist revealed genu varum and temporarily epiphysiodesis was done. After 8 months of a therapy refractory, painful soft tissue infection on one foot occurred. Despite local and systemic antimicrobial therapies a dry ulcer on the forefoot and humid necroses between the toes developed. Further diagnostic measures showed demineralization of the lower leg and tarsus as well as old fractures of the metatarsalia. Conventional angiography and angio-magnetic resonance imaging revealed an obliteration of the posterior tibial artery and high-grade stenoses of the anterior tibial artery and the fibular artery with multiple collaterals. In synopsis of the clinical and radiographic findings, a peripheral arterial occlusive disease grade 4 was diagnosed. After ineffective medicamentous and interventional attempts to improve perfusion, amputation of the lower leg was performed. Histological examination of the arterial blood vessels in the amputation stump provided evidence of changes in terms of an intima-type vasculopathy with subtotal to total stenoses due to intimal hyperplasia consistent with vascular neurofibromatosis.

Conclusion: Vascular complications in neurofibromatosis type 1 are described in literature as fibromuscular dysplasia in renal arteries and as stenoses or ectasias of the carotids or the cerebral arteries. Vasculopathies of the peripheral arteries leading to the clinical picture of a peripheral arterial occlusive disease are extremely rare, especially in childhood. Differences in length or circumference of extremities, trophic dysfunction, abnormal wound healing, or persistent pain should result in further angiologic diagnostics.