Autosomal dominant arthropathy in a French family

Many rheumatic diseases are influenced by both genetic and environmental factors. Studies of families help to understand the genetic aspects of these multifactorial disorders. Some are inherited as an autosomal dominant trait, such that an individual who inherits the gene carrying the trait will have the disease. Other rheumatic disorders such as ankylosing spondylitis (spinal arthritis which ends in spinal fusion and rigidity) tend to cluster in families, but will not occur uniformly. Spondylitis is related to the presence of a particular HLA (human leukocyte antigen) subtype. These subtypes are groups of cell-surface proteins which distinguish self cells from nonself cells and are important in defense against foreign organisms and rejection of grafted tissues. Spondylitis, similar spondylarthropathies (arthritis of the spine), and rheumatoid arthritis have not previously been found to inherited as an autosomal dominant trait. The occurrence of an arthropathy (joint disease) running within a French family is described. The study was begun after finding two sisters and a brother with a polyarthritis (involvement of many joints) without positive blood tests. Five generations and 83 family members were studied. Medical symptoms and X-ray evidence of arthritis were found in 16 subjects. Eye inflammation, intestinal disease, and psoriasis were not present. Three consecutive generations were affected, every affected subject in the second to fourth generations had an affected parent, transmission was autosomal rather than sex-linked (as male-to-male transmission was found), and 61 percent of children of affected subjects inherited the disease, all suggestive of an autosomal dominant inheritance pattern. Joint symptoms began between 18 and 32 years. The wrist, foot, or shoulder were usually the first joints involved, and the disease usually occurred as intermittent episodes of one to three months. Mechanical factors influenced the joints affected, as right-handed subjects had right-sided symptoms, and manual workers had inflamed wrists. Painless stiffness gradually developed, and the neck, low back, and sacroiliac joints were involved, but not prominently. X-rays showed bone erosions and proliferation. Joint symptoms did not resemble rheumatoid arthritis or ankylosing spondylitis. Ossification (bony changes) of soft tissues occurred. The study suggests this is a novel type of inherited arthritis, and research is needed to identify the target of the genetic change. (Consumer Summary produced by Reliance Medical Information, Inc.)