Early recognition of heterozygotes for the gene for dystrophia myotonica

Abstract

A study has been performed on 124 first degree relatives of 38 index patients with dystrophia myotonica in order to assess means of detecting heterozygotes before neurological complaints. Some or all of the following tests have been performed on the relatives: clinical examination, electromyography, slit-lamp examination, radiography of the skull, electrocardiography, serum insulin, and serum immunoglobulin levels. There is evidence that abnormalities in symptomless heterozygotes may be detected by slit-lamp examination, electromyography, and immunoglobulin concentration, and this is probably the order of usefulness of the test in early recognition of the disease. In this study 13 previously undetected heterozygotes have been identified: six as a result of neurological examination, four by both electromyography and slit-lamp examination, and three by slit-lamp examination alone. Abnormalities detected by these tests appear to be independently manifest, so that they will probably be more useful in combination than singly. The family data give a maximum estimate for incidence of mutations among index cases of one quarter, lower than previously suggested. The estimation of immunoglobulins in 45 patients showed significant deficiency, as compared with controls, not only of IgG but also of IgM, and there was an insignificant trend for IgA to be low too. This suggests that the abnormally rapid catabolism of immunoglobulin, previously reported, is not specific for IgG.