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Blisters: Blistering genodermatoses: reclassifying the old and discovering the new

Presentation Description
Every few years an international group of experts convenes to try to establish a new consensus classification for the group of inherited blistering skin diseases known as epidermolysis bullosa (EB). The need to do this reflects new basic science discoveries in identifying further genes that when mutated cause trauma-induced blistering in skin or mucosae, as well as ongoing efforts to make the classification of EB more valuable to clinicians and patients. The latest consensus classification of EB was published in October 2020. In this presentation, I will highlight the key elements of the new classification and also review new discoveries in the blistering genodermatoses. Although many of these conditions are very rare, several of the mutations identified are loss-of-function which provide fundamental data into how the encoded proteins function in healthy skin, findings which improve our understanding of normal skin structure and function. The five most recently implicated genes in skin fragility are KLHL24 (kelch-like member 24), CD151 (tetraspanin 24), PLOD3 (lysyl hydroxylase 3), DSG3 (desmoglein-3) and DSC3 (desmocollin-3). Of note, the phenotypic consequences of all these new blistering diseases are associated with additional extracutaneous abnormalities. KLHL24 mutations result in a form of autosomal dominant EB simplex in which basal keratin 14 levels are depleted through excessive turnover of the keratin, but there is also an increased risk of developing cardiomyopathy; autosomal recessive CD151 mutations also result in intra-epidermal cleavage but there is an association with nephrotic syndrome; PLOD3 mutations cause autosomal recessive sub-lamina densa blistering similar to dystrophic EB but with multiple connective tissue and skeletal defects; DSG3 is associated with autosomal recessive oropharynegeal and minor skin erosions; finally, autosomal recessive DSC3 mutations result in skin blistering and hypotrichosis. These discoveries collectively add to our understanding of the spectrum of inherited skin fragility disorders, as well as helping improve clinical management though a better appreciation of the range of cutaneous and extracutaneous pathologies that may accompany a specific gene mutation. The expanded data and new classification are also fundamental to translational research and future therapies for EB. 
Other Suggested Sessions Presentations
#Australasian College of Dermatologists Annual Scientific Meeting 2021
#Australasian College of Dermatologists Annual Scientific Meeting 2021