063 A new case series of Olmsted syndrome subjects confirms EGFR activation and shows remarkable efficacy of targeted systemic EGFR inhibition with acceptable side effects

Abstract

Olmsted syndrome (OS) is a rare, painful, and severe form of palmoplantar keratoderma (PPK). It is most often caused by dominant mutations in the transient receptor potential vanilloid-3 (TRPV3) gene, resulting in the constitutive activation of this thermosensitive calcium channel. TRPV3 signaling leads to epidermal growth factor receptor (EGFR) activation and subsequent abnormal proliferation and differentiation of keratinocytes in mice and cell lines. We previously reported that blocking EGFR transactivation with oral Erlotinib treatment resulted in remarkable improvement in 4 young patients.