Multiple self-healing squamous epithelioma (MSSE; MIM 132800), also known as Ferguson-Smith disease, is an autosomal dominant skin disorder caused by mutations in TGFBR1.  While Loeys-Dietz syndrome (LDS1A; MIM609192) and thoracic aortic aneurysms (AAT5; MIM 608967) result from gain of function mutations in TGFBR1, MSSE appears to be due to a loss of function of the TGFBR1 gene.  Reported mutations include missense changes in exon 2 within the extracellular ligand binding domain, nonsense changes, and frameshift changes.  MSSE is characterized by multiple skin lesions that clinically and histologically resemble squamous carcinoma.  These lesions grow rapidly for a few weeks starting as small papules and progressing into keratoacanthoma-like tumors with rolled edges and a central hyperkeratotic plug. After a few weeks, the tumors spontaneously regress leaving pitted scars.  In MSSE, the TGFBR1 gene appears to act as a tumor suppressor requiring a second somatic hit to produce the lesions, resulting in incomplete penetrance and highly variable age of onset.