Introduction

Primary pulmonary hypertension (PPH) is typically described as a sporadic disorder. However, patients with at least one affected relative have been increasingly recognized since early reports of the disorder over 50 years ago [1]. Interestingly, the natural history of PPH appears similar in both familial and sporadic forms of the disease. Recent advances in understanding the genetic basis of familial PPH are therefore likely to shed light on the pathogenic processes common to all forms of the disease.

Molecular genetic studies have identified that mutations within the gene BMPR2 on the long arm of chromosome 2 underlie familial PPH [2, 3]. This chapter describes the studies that led to these discoveries, explores the prospects for future research into the molecular mechanisms involved in the disease process and emphasizes the immediate implications for assessment and management of patients and their relatives, as a consequence of the identification of the gene associated with PPH.

Patterns of inheritance

Figures from the American National Institute of Health Registry demonstrate that at least 6% of patients with PPH have a family history of the disease [4]. However, familial cases may be difficult to detect due to delayed or missed diagnosis, inadequate case finding or the markedly reduced penetrance by which the disease gene acts. Hence, PPH individuals in families may inherit and transmit the disease gene without developing overt clinical features of the disease. This observation may explain the recognition of remote common ancestry occasionally observed in patients with apparently sporadic PPH [5].