Familial Scleroderma—evidence for Environmental Versus Genetic Trigger

Abstract

Families with more than one case of scleroderma are unusual. Four families each with two members (in one case monozygotic twins) with scleroderma (systemic sclerosis, SSc) were identified. Clinical, immunogenetic and autoantibody studies were carried out. Multicase SSc families cited in the literature were reviewed. Each family pair shared cutaneous subset of disease severity, and SSc-associated autoantibody. HLA typing showed two pairs shared an HLA-DR allele associated with scleroderma (DR3 or DR5), while one also had alleles reported in association with their SSc-specific autoantibody. Review of dates and ages of onset suggested that the timing of onset of scleroderma is more likely to have an environmental trigger than to be encoded genetically.

Familial scleroderma: nature, nurture or both?

“…This was independent of ‘disease onset’ definition. These findings are in contrast to those previously published 19 . There were some interesting trends, however, and one statistically significant result.…”

“…However, the argument that increased familial disease risk supports a genetic hypothesis, or, conversely, that increased familial risk supports an environmental hypothesis, is fundamentally flawed, because families share both a similar gene pool and usually a common environment at least till young adulthood. A previous study by Stephens et al , describing four multicase families and a meta‐analysis of 20 familial scleroderma clusters, reported smaller (although statistically non‐significant) differences in dates at disease onset than ages at disease onset in parent–child affected pairs 19 . These results supported an environmental contribution to disease aetiopathogenesis.…”

Systemic sclerosis in two second cousins: a case report

“…Systemic sclerosis has different manifestations, which may or may not have familial links. 5 In our cases, a relative had autoimmune disease. Many studies have investigated systemic sclerosis and MHC antigens, but the pattern of association is still not clear.…”

Genetics and proteomics in scleroderma

“…A second report describes four families each with two members with scleroderma. Two families had affected siblings, a mother-daughter pair, and a father-daughter pair [24]. Two other reports of familial scleroderma in South Carolina have been documented within close geographic proximity.…”