Abstract

A heritable basis to pulmonary arterial hypertension (PAH) was initially observed by Dresdale in 1954. Familial clustering has since been recorded in approximately 10% of the patient population although, due to the complex features of inheritance in PAH, it is widely acknowledged that the proportion of patients with one or more affected relatives is likely to be higher. Indeed, familial PAH has since been reclassified as heritable or HPAH in light of the fact that a germline genetic defect may be transmissible to future generations in as many as a third of all cases. In the majority of cases, PAH is idiopathic arising spontaneously without familial sharing and without a detectable underlying genetic cause. PAH may occur in association with known risk factors, for example, fenfluramine and dexfenfluramine derived appetite suppressant drugs, or other disorders including thromboembolic disease, connective tissue disease, congenital heart disorders and human immunodeficiency virus (HIV) infection. The classical features of vasoconstriction and pulmonary arteriole remodelling are observed in all forms of PAH, suggesting a common aetiology although shared disease pathways remain to be fully elucidated.