Familial primary pulmonary hypertension is a rare, progressive, autosomal dominant disease characterized by monoclonal plexiform lesions of proliferating endothelial cells in pulmonary arterioles, leading to elevated pulmonary-artery pressures, right-ventricular failure, and death. The disease can occur from infancy throughout life; it has a mean age at onset of 36 years, and the ratio of affected females to affected males is 2:1. The average life expectancy after diagnosis is two to three years with death usually due to progressive right heart failure. The pathogenesis of primary pulmonary hypertension is unknown. Although most cases appear to be sporadic, approximately 6% of cases are inherited in an autosomal dominant manner with high, but incomplete penetrance.
By linkage analysis, the localization of the gene familial primary pulmonary hypertension gene could be identified to a locus on chromosome 2q33. Mutations in the bone morphogenetic protein type II receptor (BMPR2) gene causes familial primary pulmonary hypertension. Germline mutations of BMPR2 are also found in >26% of sporadic cases of primary pulmonary hypertension. Primary pulmonary hypertension may also be found in association with hereditary hemorrhagic telangiectasia type 1&2, which is caused by mutation in the ENG gene and ACVRL1 gene, respectively.