In 1985, Strom et al described two families in which
rheumatoid arthritis (RA) appeared in several members
over three consecutive generations.' Although these pedigrees taken alone could implicate dominant inheritance,
the overall picture with RA pedigrees indicates a complex
mode of inheritance, with incomplete penetrance of
predisposing genes and probably several genes being
involved in the diseases process. In addition, an interesting
observation in both pedigrees described by Strom's group
and one which is difficult to understand in terms of
classical Mendelian genetics is that the disease tended to
start progressively earlier over the generations (60 to 81
years in the grandparents, 36 to 47 in the parents, and 12
to 28 in the probands). For both families, the clinical
details of the individuals suggested that not only was the
disease starting earlier, but it was also becoming more
severe over the generations.' Is there any possible
explanation for this observation, and does this anecdote
have any potential repercussions for our understanding of
the genetics of the rheumatic diseases?