Genetic Factors in Generalized Osteo-arthrosis.

The occurrence of osteo-arthrosis in multiple joints was noted by Adams (1857). Cecil and Archer (1926) observed that the condition was more often polyarticular than monarticular in patients attending their rheumatism clinic, occurred mainly in middle-aged females, and was usually associated with Heberden's nodes; they labelled the condition menopausal arthritis. Stecher (1941, 1955) investigated the families of 64 patients with Heberden's nodes, and found the condition twice as frequently in the mothers and three times as frequently in the sisters of affected women as in the general population. He postulated that the nodes were inherited as a Mendelian dominant in females and as a recessive in males. It was apparent from his findings that arthrosis of the distal interphalangeal joints of the fingers had a hereditary basis. Although the proximal interphalangeal joints of the fingers were involved in 25 per cent. of Stecher's cases, he did not find clinical evidence of any association with osteo-arthrosis of other joints. Kellgren and Moore (1952), on the other hand, from a study of 391 patients with osteo-arthrosis attending a rheumatism clinic, found evidence ofan association of Heberden's nodes with a distinct pattern of joint involvement, including the first carpometacarpals. the proximal interphalangeals, the apophyseal joints of the spine, the knees, and the first tarsometatarsals. This association of Heberden's nodes with multiple osteo-arthrosis was later confirmed by x-ray studies on a random sample of the population of Leigh, Lancs., and the characteristic pattern of joint involvement was corroborated (Kellgren and Lawrence, 1958). Whilst indirect evidence of a hereditary basis for a generalized form of osteo-arthrosis was thus forthcoming, it was felt that this should be confirmed by a direct approach and that steps should be taken to discover whether the mode of inheritance postulated by Stecher for Heberden's nodes also applied to this generalized form of osteoarthrosis. In addition, it was felt that other forms of multiple osteo-arthrosis of varying aetiology might exist, some associated with occupation, others with a genetic factor. Certain rare forms are already known to occur, for example the type associated with ochronosis, and the multiple osteo-arthrosis associated with gout may well be more frequent than is generally supposed. Rheumatoid arthritis has also been postulated as a cause of osteo-arthrosis. An inherited tendency to multiple osteo-arthrosis is also known to exist in certain strains of laboratory animals and these have been studied extensively (Silberberg and Silberberg, 1955; Sokoloff, Mickelsen, Silverstein, Jay, and Yamamoto, 1960; Sokoloff, Crittenden, Yamamoto, and Jay, 1962).