HEBERDEN'S NODES: THE MECHANISM OF INHERITANCE IN HYPERTROPHIC ARTHRITIS OF THE FINGERS 1

Abstract

Heberden''s nodes, a form of hypertrophic arthritis, are enlargements of the terminal interphalangeal joints of the fingers. The trait comes to expression ordinarily in middle life or early old age; the mean age of onset is about 48.5 yrs. That Heberden''s nodes are hereditary is shown by the strong tendency to bilateral symmetry and by the greater incidence in close relatives of affected individuals than in the general population. Similar nodes caused by trauma are readily distinguished from the hereditary form and have a different history. Heberden''s nodes show certain peculiarities from the genetic point of view, namely, (1) at an advanced age when penetrance is complete there is a great preponderance among women in the general population, about 30% as compared to about 3% of men, (2) multiple involvement among sisters without brothers being affected, (3) transmission through [female][female] in a manner which frequently resembles matrilineal inheritance, (4) a greater frequency in families with affected mothers, (5) fathers rarely affected, (6) an approximation to a 1:1 ratio among daughters in families with neither parent affected, (7) a high incidence among sisters of affected men. The analysis of 74 pedigrees shows on the basis of numerical tests that the entire body of data and observations are in good agreement with the hypothesis that the genetic cause of Heberden''s nodes is a single autoaomal gene, dominant in [female][female], recessive in [male][male]. The gene frequency analysis reveals in the general population 2.7% homozygous for the gene, 27.2% heterozygotes and 70% homozygous recessive normals.