HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Full Text (PDF) Free All Versions of this Article: chest.06-3017v1 chest.06-3017v2 132/3/798    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stewart, D. R. Articles by Ross, D. J. Search for Related Content PubMed PubMed Citation Articles by Stewart, D. R. Articles by Ross, D. J.

Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy?

¹National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, MD, USA ²Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA ³Institute of Pulmonary Medicine, Rabin Medical Center, Petach Tikva, Israel ⁴Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA ⁵St. Joseph's Hospital, Reading PA, USA ⁶Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA ⁷Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA ⁸Lung Center of Nevada, Las Vegas, NV, USA ⁹Division of Pulmonary and Critical Care Medicine, University of Washington and Veterans Administration Medical Center, Boise ID, USA ¹⁰Departments of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA ¹¹Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA ¹²First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan ¹³Department of Pathology and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA ¹⁴Department of Pulmonary and Critical Care Medicine and Hospitalists, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

drstewart{at}mail.nih.gov

Abstract

BackgroundNeurofibromatosis 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 NF1 is hypothesized to be secondary to an underlying vasculopathy.

MethodsWe describe the entity we term NF1-associated pulmonary arterial hypertension (NF1-PAH) in four new patients and update four previously-published patients. We performed genetic testing of BMPR2, the gene mutated in 70% of patients with familial PAH and approximately 25% of patients with idiopathic pulmonary arterial hypertension. We report, for the first time, pathologic findings in the autopsy-obtained lung of one patient with NF1 and PAH.

ResultsPatients with NF1-PAH have a generally poor long-term prognosis. In four patients we observed the mosaic pattern of lung attenuation on computed tomography of the chest, a radiographic finding that can be consistent with an underlying vasculopathy. No mutations or rearrangements in BMPR2 were found. We observed complex plexiform lesions in the one available autopsy specimen. Similar lesions are a hallmark of plexogenic pulmonary arteriopathy and associated with several severe types of PAH. (Plexiform lesions should not be confused with plexiform neurofibromas, distinctive tumors seen in NF1.)

ConclusionsOur findings suggest that neurofibromatosis type 1 should be considered as "associated with pulmonary arterial hypertension (APAH)" as outlined in the Revised Clinical Classification of Pulmonary Hypertension. Understanding the mechanism of PAH in NF1 may inform the pathogenesis PAH, NF1-PAH itself and other NF1-associated vasculopathies. The pulmonary vasculature should now be included among the arterial beds affected by NF1 vasculopathy.

Key Words: Neurofibromatosis type 1 • Plexiform arteriopathy • Vasculopathy • Mosaic perfusion pattern of lung attenuation • Bone morphogenic protein 2 (BMPR2)