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Estimating the frequency of familial dilated cardiomyopathy in the presence of misclassification errors

Dilated cardiomyopathy is a disease of unknown cause characterized by dilation and impaired function of one or both ventricles. Most cases are believed to be sporadic, although familial forms have been detected. The familial form has been estimated to have a relative frequency of about 25%. Since, except for familial history, familial form has no other characteristics that could help in classifying the two diseases, the estimate of the frequency of the familial form should take into account a possible misclassification error. In our study, 100 cases were randomly selected in a prospective series of 350 patients. Out of them, 28 index cases were included in the analysis: 12 were known to be familial, and 88 were believed to be sporadic. After extensive clinical examination of the relatives, 3 patients supposed to have a sporadic form were found to have a familial form. 13 cases had a confirmed sporadic disease. Models in the Log-Linear Product class (LLP) have been used to separate classification errors from underlying patterns of disease incidence. The most conservative crude estimate of the misclassification error is 16.1% (CI 0.22- 23.27%), which leads to a crude estimate of the frequency of the familiar form of about 60%. An estimate of the disease frequency, adjusted for taking into consideration the sampling plan, is 40.93% (CI 32.29-44.17%). The results are consistent with the hypothesis that genetic factors are still underestimated, although they represent a major cause of the disease.