EASL Clinical Practice Guidelines

Family screening

It is essential to screen the family of patients presenting with Wilson's disease because the chance of a sibling being a homozygote – and therefore developing clinical disease – is 25%. Amongst offspring, the chance is 0.5%. Although this risk is low, analysis of the ATP7B gene for mutations in the children of an index patient is justified given the potential devastating course of Wilson's disease. There is difficulty in diagnosing heterozygote carriers with certainty, but siblings of an index case with a documented mutation can be screened by mutational analysis.

If the mutation(s) of the index case are not detected, pedigree analysis using haplotypes based on polymorphisms surrounding the Wilson's disease gene is available. This analysis requires the identification of an index patient with the unquestionable diagnosis of Wilson's disease within the family. DNA is required from both parents. Then the haplotype, based on the pattern of dinucleotide and trinucleotide repeats around ATP7B, is determined in the index patient and his/her family. The inheritance of the “disease-associated" haplotypes allows determining whether they are unaffected, heterozygous, or indeed patients [78]. Genetic testing is the only reliable method to separate heterozygote from homozygote siblings.