The variant c.1670G>A in the SREBF1 gene is associated with unusual clinical manifestations of IFAP syndrome

Ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome is a rare genetic genodermatosis. According to previous reports, in addition to MBTPS2 variants, variants in SREBF1 (encoding SREBP1) can also cause IFAP syndrome. SREBF1 variants can also result in hereditary mucoepithelial dysplasia (HMD). These two diseases exhibit some similar clinical features. We report two cases of IFAP syndrome with atypical clinical features associated with the c.1670G>A variant in the SREBF1 gene, and review the clinical characteristics of all reported cases of IFAP syndrome and HMD patients with SREBF1 variants to date. Whole-exome sequencing was performed for the two patients, and immunohistochemistry was performed on samples from psoriatic-like plaques on the right lower limb of one of the patients. A PubMed search was conducted to identify all patients with IFAP syndrome and HMD with SREBF1 variants. A missense variant c.1670G>A in SREBF1 was identified in our two patients. The heterozygous SREBF1 variant was not identified in their parents. Immunohistochemistry of samples from the psoriatic-like plaques on the lower limb from one of the patients showed enhanced staining for IL-17A and S100A8, with reduced nuclear translocation of SREBP1. We describe two cases of IFAP syndrome without apparent photophobia, one of which exhibited severe psoriasis-like plaques limited to the extensor sides of both lower limbs. Immunohistochemical results of the lower limb lesions showed partial resemblance to psoriatic lesions. In addition, a comparative review of the clinical features of all published HMD and IFAP syndrome cases is presented.