Cardiovascular disease in neurofibromatosis 1: Report of the NF1 Cardiovascular Task Force

Abstract

Purpose: Patients with neurofibromatosis 1 (NF1) are at increased risk for a variety of cardiovascular disorders, but the natural history and pathogenesis of these abnormalities are poorly understood. Methods: The National Neurofibromatosis Foundation convened an expert task force to review current knowledge about cardiovascular manifestations of NF1 and to make recommendations regarding clinical management and research priorities related to these features of the disease. Results: This report summarizes the NF1 Cardiovascular Task Force's current understanding of vasculopathy, hypertension, and congenital heart defects that occur in association with Key Words: neurofibromatosis 1, vasculopathy, hypertension, congenital heart defects Neurofibromatosis 1 (NF1), an autosomal dominant disease, is one of the most common mendelian disorders. 1 It is characterized by extremely variable expressivity, but most patients have café-au-lait spots, intertriginous freckling, dermal and plexiform neurofibromas, and learning disabilities. 2 People with NF1 may also develop cardiac and vascular disease, but the frequency, natural history, and pathogenesis of these abnormalities are uncertain. The National Neurofibromatosis Foundation convened an expert panel, the NF1 Cardiovascular Task Force, to review current knowledge about the cardiovascular manifestations of NF1 and to make recommendations regarding clinical management and research priorities. This is the report of that Task Force.Neurofibromas, the characteristic tumors of NF1, can develop within the heart, obstruct blood flow in the heart or major vessels by compression or invasion, or erode a vessel and cause hemorrhage. Fortunately, these are rare complications. This report will concentrate on the three most common cardiovascular manifestations of NF1, viz., vasculopathy, hypertension, and congenital heart defects.People with NF1 constitute a substantial fraction of all patients with dysplastic renal artery stenosis, 3 early-onset cerebrovascular disease, 4 or pheochromocytomas, 5 and cardiovascular disease is a frequent cause of premature death in individuals with NF1. Sørensen and associates 6 found that myocardial infarction and cerebrovascular accidents often occurred at a younger than expected age among NF1 patients. Zöller et al. 7 reported that cardiovascular disease, hemorrhage, and embolism were frequent causes of death in 70 adult NF1 patients who were followed for 12 years. Hypertension was significantly associated with mortality, and the mean age at death among the NF1 patients was approximately 14 years younger than expected. The median age of death reported on death certificates of 3,253 individuals with probable NF1 was approximately 15 years less than expected in another study. 8 Diagnoses suggestive of NF1 vasculopathy were listed 7.2 times more often than expected among NF1 patients Ͻ 30 years old and 2.2 times more often than expected among those who were 30 to 40 years old at the time of death. NF1 VASCULOPATHY Epidemiology and clinical featuresNF1 c...

Neurofibromatosis 1

“…24 Neurofibromatous vasculopathy affects both arterial and venous circulations in the brain and manifestations include cerebral artery stenosis or occlusion, aneurysm and rupture. 25 Cerebral haemorrhage accounts for 50% of deaths owing to cerebrovascular disease in Nf1. 26 Multiple sclerosis and epilepsy (predominantly complex partial seizures) have been observed in association with Nf1, the latter probably arising from an underlying cortical dysgenesis.…”

“…There is a higher than expected frequency of congenital heart disease in Nf1 individuals, particularly of valvular pulmonary stenosis. 6,25 Orthopaedic problems Orthopaedic complications result from intrinsic defects of the skeletal system and from a disruption of bone structure maintenance. 29 Bone mineral density is decreased in Nf1 patients, mainly in the load bearing parts.…”

Neurofibromatosis: part 2 – clinical management

“…These observations could be related to NF1 shorter life expectancy, the poorer quality of life and the more frequent and earlier cardiovascular involvement observed in NF1, when compared to the general population 9 .…”

“…Vasculopathy is an important cause of death in younger age groups 6 and it is an important cause of sudden death in asymptomatic patients 9 , caused mainly by vascular fibromuscular dysplasia and malformations 10 rather than atherosclerotic related conditions 11 .…”

Ruptured Extracranial Vertebral Artery Aneurysm Associated With Neurofibromatosis Type 1

“…The frequency of vascular lesions in NF1 patients is hard to define because screening studies are not routinely performed, but the prevalence of vascular lesions in large series is 0.4% to 6.4%. 3,4,11,14) Renal artery lesions are most common (41%) and are more often stenotic than aneurysmal, but carotid artery, vertebral artery (VA), and cerebral artery aneurysms, reported in 46 patients, occur in the third decade of life and are more common in women. The renal artery is most frequently involved, resulting in renovascular hypertension.…”