Phenotypic Expansion of Autosomal Dominant SREBF1 ‐Related Ichthyosis Follicularis, Atrichia, Photophobia: It Is in Fact the Same Condition as Hereditary Mucoepithelial Dysplasia

Hereditary mucoepithelial dysplasia (HMD) is a rare autosomal dominant disorder characterized by non-scarring alopecia, skin and mucosal lesions, and keratitis. Autosomal dominant SREBF1-related Ichthyosis Follicularis, Atrichia, Photophobia (IFAP) syndrome is another rare, similar disorder. Both are now known to be caused by the same NM_004176.5(SREBF1):c.1579C>T variant, but were previously described as separate disorders. Here, we describe a case series of four novel patients that we diagnosed with SREBF1-related IFAP due to the NM_004176.5(SREBF1):c.1579C>T variant. We also performed a literature review and applied the ClinGen Lumping and Splitting criteria to these two disorders. Three of our four patients had significant gastrointestinal manifestations including gastroesophageal reflux disease and esophageal strictures/webs. To date, no gastrointestinal manifestations have been described in SREBF1-related IFAP. There are, however, multiple reports of these manifestations in cases of HMD. Applying the ClinGen Lumping and Splitting criteria demonstrated that these two previously distinct disorders are actually favored to be "lumped" into one. Taken together, a documented overlap in clinical features, the shared variant, and the gastrointestinal manifestations of our SREBF1-related IFAP patients provide evidence that HMD and SREBF1-related IFAP better represent variable expressivity of the same disorder. We propose using the unifying name of "SREBF1-syndromic epidermal differentiation disorder" (SREBF1-sEDD).