Two sporadic cases of childhood-onset Hailey-Hailey disease with superimposed mosaicism

A prenatal second-hit genetic change that occurs on the wild-type allele in an embryo with a congenital pathogenic variant allele results in mosaicism of monoallelic and biallelic defect of the gene, which is called superimposed mosaicism. Superimposed mosaicism of Hailey-Hailey disease (HHD) has been demonstrated in one familial case. Here, we report two unrelated HHD cases with superimposed mosaicism: a congenital monoallelic pathogenic variant of ATP2C1, followed by a postzygotic copy-neutral loss of heterozygosity. Uniquely, neither patient had a family history of HHD at the time of presentation. In the first case, the congenital pathogenic variant had occurred de novo. In the second case, the father had the pathogenic variant but had not yet developed skin symptoms. Our cases showed that superimposed mosaicism in HHD can lack a family history and that genetic analysis is crucial to classify the type of mosaicism and evaluate the risk of familial occurrence.

Automated summary

A prenatal genetic change on the wild-type allele in an embryo with a congenital pathogenic variant allele can cause superimposed mosaicism of monoallelic and biallelic defect of the gene. We report two HHD cases with superimposed mosaicism: a congenital monoallelic pathogenic variant followed by a postzygotic copy-neutral loss of heterozygosity. Our cases showed that superimposed mosaicism in HHD can occur without a family history and genetic analysis is crucial for evaluating the risk of familial occurrence.