Familial primary pulmonary hypertension: clinical patterns

We recently identified a family with 6 deaths in 2 generations from primary pulmonary hypertension. The disease was undiagnosed in several of them, and the family members, geographically separated, were unaware that there was a familial disease. We hypothesized that familial primary pulmonary hypertension (FPPH) might be labeled as nonfamilial in situations where the family history was incomplete. In order to better define the clinical patterns of transmission of known FPPH, we surveyed as many of the previously reported families as possible (9 of 13) and found 8 new cases in 5 of these families. Looking at all cases, the most important finding was the infrequent expression of the gene within some families and the widely differing frequency of expression among families. The pattern was autosomal dominant with a 2:1 female-to-male ratio. One instance of male-to-male transmission excluded x-linkage of the gene. Survival after onset of symptoms was the same as that reported for nonfamilial primary pulmonary hypertension (PPH). We conclude that many apparently nonfamilial cases of PPH may actually have the same etiology as in FPPH.