Comparison of key distinguishing features between pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with neurofibromatosis type 1 (PH-NF1)

Idiopathic or heritable PAHPH-NF1
 Main gene mutationBMPR2, ACVRL1, ENG, KCNK3, CAV-1, SMAD9NF1
 Genetic transmissionAutosomal dominantAutosomal dominant
 Estimated prevalence15 cases per millionPrevalence of NF1 is 1 per 3000, prevalence of PH is unknown
 Sex ratioFemale predominance (∼2:1)Female predominance (∼4:1)
Clinical examination
 Dermatological signsAbsentCafé au lait macules, axillary or groin freckling, subcutaneous neurofibroma
 Neurological signsAbsentPossible optic glioma
Right heart catheterisation
 mPpa, PAWP, PVRIncreased mPpa, normal PAWP, increased PVRMore severely increased mPpa, normal PAWP, more severely increased PVR
 Acute vasoreactivity testing∼10% in idiopathic PAH (predicts long-term CCB response)No case reported
Pulmonary function
 FEV1, FVC, TLCNormal (possible mild reduction)Normal (possible mild reduction)
DLCONormal (possible mild reduction)Severe reduction
 Chest HRCTUsually normal parenchymaGround-glass opacities, lung cysts, lung reticulations
V′/Q′ lung scanUsually normalUsually normal
 Targeted PAH therapyImproved haemodynamics, functional capacity and clinical outcomesPoor response (based on isolated case reports)

BMPR2: bone morphogenetic protein receptor type 2; ACVRL1: activin A receptor type II-like kinase 1; ENG: endoglin; KCNK3: potassium channel subfamily K member 3; CAV-1: caveolin 1; mPpa: mean pulmonary artery pressure; PAWP: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLC: total lung capacity; DLCO: diffusing capacity of the lung for carbon monoxide; HRCT: high-resolution computed tomography; V′/Q′: ventilation/perfusion; CCB: calcium channel blocker.