BACKGROUND: Neurofibromatosis type 1 (NF1) is a common disorder of dysregulated 
tissue growth secondary to mutations in the tumor suppressor gene NF1. Pulmonary 
arterial hypertension (PAH) in patients with NF1 is hypothesized to be secondary 
to an underlying vasculopathy.
METHODS: We describe the entity we term NF1-associated PAH (NF1-PAH) in four new 
patients and update the data on four previously published reports of patients 
with PAH and NF1. We performed genetic testing of the bone morphogenic protein 
receptor 2 (BMPR2) gene, which mutated in 70% of patients with familial PAH and 
approximately 25% of patients with idiopathic PAH. We report, for the first 
time, pathologic findings in the autopsy-obtained lung of one patient with 
NF1-PAH.
RESULTS: Patients with NF1-PAH have a generally poor long-term prognosis. In 
four patients, we observed the mosaic pattern of lung attenuation on a CT scan 
of the chest, a radiographic finding that can be consistent with an underlying 
vasculopathy. No mutations or rearrangements in the BMPR2 gene were found. We 
observed complex plexiform lesions in the one available autopsy specimen. 
Similar lesions are a hallmark of plexogenic pulmonary arteriopathy and are 
associated with several severe types of PAH. (Plexiform lesions should not be 
confused with plexiform neurofibromas, which are distinctive tumors seen in 
NF1.)
CONCLUSIONS: Our findings suggest that NF1 should be considered as being 
"associated with PAH as outlined in the Revised Clinical Classification of 
Pulmonary Hypertension. Understanding the mechanism of PAH in NF1 may inform the 
pathogenesis of PAH, NF1-PAH itself, and other NF1-associated vasculopathies. 
The pulmonary vasculature should now be included among the arterial beds 
affected by NF1 vasculopathy.