Individuals heterozygous for C1R- or C1S-null mutations are reported to be asymptomatic, and in particular have not been reported to have periodontal disease.13, 23, 26 Loss of C1 esterase inhibitor results in intermittent and sometimes life-threatening angioedema due to excessive bradykinin production linked to an off-target effect of activated C1s.27 This evidence concerns the gene C1R and angioedema.