Chest
ORIGINAL RESEARCHPULMONARY HYPERTENSIONIs Pulmonary Arterial Hypertension in Neurofibromatosis Type 1 Secondary to a Plexogenic Arteriopathy?
Section snippets
Case Reports
Table 1 summarizes the clinical evaluation of four previously unreported patients with NF1 and PAH. Table 2, Table 3 summarize detailed echocardiographic and cardiac catheterization data. All patients underwent an appropriate workup to rule out secondary causes of pulmonary hypertension.
Materials and Methods
All investigations were performed under protocols approved by the University of Pennsylvania School of Medicine, Vanderbilt University School of Medicine, Cincinnati Children's Hospital Medical Center, and the National Human Genome Research Institute institutional review boards.
Patient 1
Complementary DNA sequencing of fragment 2 identified a single-nucleotide insertion in exon 13: 2034dupC. The mutation was confirmed by sequencing exon 13 in genomic DNA.
Mutations in BMPR2
All samples had a wild-type sequence only for BMPR2 without evidence of rearrangements. In patient 1, a rare (minor allele frequency, 2%), nonconservative single-nucleotide polymorphism (rs2228545; c.2324G>A; p.Ser775Asn) in exon 12 was found.
Summary of NF1-PAH Phenotype
Detailed phenotype data are available in nine patients (Table 4), and detailed
Discussion
NF1-PAH is a rare complication of a classic Mendelian disorder. We provide radiographic and pathologic evidence of an underlying pulmonary vasculopathy in patients with NF1 and infer causality with the observed PAH. Despite the rarity of NF1-PAH, the association of NF1 and PAH is informative since it implicates mutations in the tumor suppressor gene NF1 with the pathogenesis of a pulmonary vasculopathy and subsequent pulmonary hypertension. Similar insights have been gleaned from other genetic
ACKNOWLEDGMENT
We thank Caroline Moore, MS, for help with cell cultures, Lisa Wheeler for administrative assistance, Grisel Lopez, MD, and Reiko Horai, PhD, for translations, and Mark Bryant, DVM, for discussions regarding the pathology findings.
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2022, Revista Portuguesa de CardiologiaPulmonary arterial hypertension: A rare yet fatal complication of Neurofibromatosis Type 1
2019, Respiratory Medicine Case ReportsCitation Excerpt :PAH in NF1 is characterized by pulmonary artery pressure >25 mm Hg, pulmonary capillary wedge pressure ≤15 mm Hg, and pulmonary vascular resistance of 240 dyn/s/cm [6,15,16]. Patients with PAH and pulmonary arteriopathy associated with NF1 usually have a relatively poor long-term prognosis [9]. In addition to malignant peripheral nerve sheath tumors, vasculopathy is one of the most important causes of early death in patients with NF1 [8].
Severe dyspnea in a patient with neurofibromatosis type 1
2017, Respiratory Medicine Case ReportsCitation Excerpt :NF1-PAH is an extremely severe complication of NF1 characterized by late onset, female predominance, severe hemodynamic impairment, poor response to PAH-specific therapy and poor outcome [11]. To the best of our knowledge, only twenty-one cases of NF1-associated PAH have been reported [11–19]. As these cases are rare and the underlying mechanisms are unclear and multifactorial, this entity has been listed in group 5 of the PH clinical classification [20].
Pulmonary arterial hypertension in von recklinghausen's disease
2015, American Journal of Medicine
This work was performed at the University of Pennsylvania, the National Human Genome Research Institute, Vanderbilt University Medical Center and University of Alabama at Birmingham.
The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of commercial products or organizations imply endorsement by the US Government.
This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, and program project grant WCN P01 HL072058.
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.