In this study, we reported two siblings with a 1.69 Mb maternally inherited microdeletion at Xp22.31 involving the genes <i>VCX3A, HDHD1, STS, VCX, VCX2</i>, and <i>PNPLA4</i> presenting with easily controlled focal epilepsy and language delay with mild ichthyosis in a Chinese family with a traceable 4-generation history of skin ichthyosis. The gene discussed is PNPLA4; the disease is ichthyosis.