Familial risk estimation in systemic sclerosis

Background: Familial systemic sclerosis has been rarely reported. Assumptio ns have therefore been made implying no familial disease aggregation. This study critically challenges the assumption using a methodical population-ba sed epidemiological approach to quantify the prevalence and characteristics of familial systemic sclerosis. Methods: In this retrospective cohort study the systemic sclerosis prevalen ce in first degree family members was compared between 715 systemic scleros is patients (710 families) and 371 randomly ascertained age and gender grou p-matched general practice controls (371 families). These data, obtained by telephone questionnaire (living patients) or medical records review (decea sed patients and untraceable patients of unknown living status), were valid ated, where necessary, and expressed in terms of relative risk, absolute ri sk and population point prevalence. Results: Systemic sclerosis affecting first degree members was validated in ten of 710 families. Reporting of systemic disease in another four more di stant family members, and the co-occurrence of systemic and localised disea se in three families was also documented. Observed and expected disease subtype concordance was 80% (44-97%) and 68% respectively and the female predominance among familial cases was similar t o that for non-familial disease. The risk of disease in a subsequent first degree relative was compared to the risk in an initial first degree family member. Its estimated magnitude was wide (11-158). However, use of populati on prevalence data to determine the expected number of systemic sclerosis p atients in the negative cohorts' families suggests the higher estimate is m ore realistic. Despite the high magnitude, the absolute disease risk in fir st degree family members remained low - approximating 1%. The population pr evalence of familial systemic sclerosis approximated 1.4/million. Conclusions: This study substantially increases the otherwise small list of documented instances of familial systemic sclerosis. More importantly, it quantifies the risk for the first time, ranking it as the disease's most po werful determinant identified to date.