Bazex-Dupré-Christol Syndrome Without Basal Cell Carcinoma Associated With a Large Interstitial Duplication at Xq26.1

Bazex-Dupré-Christol syndrome (BDCS) is a very rare genetic disorder characterized by congenital hypotrichosis, follicular atrophoderma, and early-onset multiple basal cell neoplasms. We describe an extended three-generation family with BDCS-like presentations. Affected members showed variable generalized milia and follicular atrophoderma but, notably, no hypotrichosis and no basal cell carcinomas (BCC) even for the older individuals. Whole-genome sequencing on the genomic DNA from the peripheral blood sample of the index patient using the Oxford Nanopore Technologies platform identified a 218 kb interstitial duplication at Xq26.1 involving partial duplication of two genes and the entire intergenic region, larger than the eight previously reported cases with molecular confirmation. The patient, her affected father, the father's affected sister's son all have the same duplication, while her unaffected mother does not have this duplication. Our analysis shows that the duplication segregates with the phenotype in this extended family. The duplication for this family includes the entire intergenic region with partial duplication of the two flanking genes, ARHGAP36 and IGSF1. The duplication segregates with an attenuated, forme fruste phenotype lacking hypotrichosis and BCC, suggesting duplication size and gene content may modulate disease expression. Functional studies and long-term follow-up are needed to clarify BCC risk.