Objectives: Screening for celiac disease (CD) in the apparently healthy members of 107 nuclear families with two affected siblings (sib pair) and estimating the risk of CD in siblings and parents.
Methods: One hundred seven families from Sweden and southern Norway with at least two affected children were investigated. Frozen sera from 187 of the 192 healthy parents and from 94 of 95 siblings without diagnosed CD were examined for total immunoglobulin A (IgA) and anti-endomysial antibodies (EMA). Individuals with positive antibody titers underwent small intestinal biopsy.
Results: Positive test for EMA was found in 6 of 94 (6.3%) siblings without previously diagnosed CD and in 8 of 189 (4.2%) parents. CD was confirmed by small intestinal biopsy in all siblings and seven parents. The estimated risk for CD in multiply affected families was 26.3% for siblings and 12.9% for parents. An unexpected male preponderance was found among the new CD cases (10 males, 3 females).
Conclusion: The risk of CD in the members of nuclear families with two affected children is approximately three times higher than that when only one child is affected. The high male preponderance of new cases is unexpected and could not be explained fully by more silent disease in males as compared with females. Considering the high level of knowledge about CD in these families, the number of undiagnosed cases is surprisingly high. The authors suggest that serologic screening should be offered to all first-degree relatives of patients with CD.
Celiac disease (CD) is a genetically driven immunologic intolerance to dietary gluten (1). The clinical severity is variable and includes severely affected young children, children and adults with milder symptoms, and patients with silent CD who have no symptoms at all (2). The silent group is diagnosed primarily by screening of risk groups or populations. In Sweden, childhood CD was increasingly diagnosed in the 1980s and early 1990s (3-5), and today the disease is one of the most common chronic diseases in Swedish children, surpassed only by asthma and allergies.
Screening studies in Sweden, Norway, and other countries have shown prevalence figures for CD varying between 2 and 6 per 1,000. In some studies prevalence is as high as 10 per 1,000 (6-12). However, most studies are relatively small, and the results do not differ significantly among different studies (13). In family studies, prevalence rates more than 10 times higher (2.6% to 12.2%) have been reported among siblings of patients with CD (Table 1) (14,15). Reports on the prevalence of CD in parents have varied between 0 and 6.3% (15-22) (Table 1). Twins studies have shown a concordance rate in monozygotic twins of at least 86.5% and 23% in dizygotic twins (23).
According to Falconer's theory, the risk for siblings and parents to be affected in polygenic diseases is higher in families with multiple cases than in single-case families (24,25). To our knowledge this hypothesis has never been confirmed for CD. The aim of this study was to screen for CD in apparently healthy members of nuclear families with two affected siblings (sib pair) and to estimate the risk for CD in the remaining siblings and parents.