Multiple Self-Healing Squamous Epithelioma and Loeys-Dietz syndrome: a single TGFBR1 variant, two phenotypes in one patient.

Abstract

Multiple Self-Healing Squamous Epithelioma of Ferguson-Smith (OMIM 132800) is a syndrome increasing the risk of developing keratoacanthomas, which are locally aggressive skin tumours. Loeys-Dietz syndrome is a connective tissue disease characterised by arterial fragility. There is no increased risk of skin tumours classically described.Both phenotypes have been associated with a different pathogenic variant of the TGFBR1 gene involved in the TGFbeta signalling pathway. We present the case of a patient with both phenotypes. This appears to be caused by a single likely pathogenic variant within TGFBR1: c.1421G>A (p.Cyst474Tyr) in the protein domain of the serine-threonine protein kinase.This is the fourth reported case exhibiting this dual clinical presentation with a single genetic variant in this same region.