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KELOIDS IN RTS - AND OTHER HEREDITARY SYNDROMES Cecilie Bredrup Department of Ophthalmology Haukeland University Hospital KELOIDS Proliferative fibrous growths resulting from excessive tissue response Continuous growth invasively beyond the confines of the original wound Histologically collagen fibers (type I and III) randomly orientated. Fibroblasts (cultured skin cells) show excessive extracellular matrix production and altered behavior Treatment is dif ficult, recurrence is high KELOIDS Keloids occur in all ethnic groups but are more common in individuals with dark skin, most frequently in individuals aged 11-30 years. Most commonly chest, shoulders, upper back and ears Puberty/pregnancy increased risk Genetic predisposition plays a major role in keloid development (ethnicities, families, twins) Pathogenesis remains largely unknown Animal models limited value A small number of congenital disorders also have keloids, RTS is the most frequent Aesthetic disfigurement, impaired function due to restricted skin/joint mobility, pain and itching TREATMENT OPTIONS Non-targeted therapies Surgery alone (70-100% recurrence) In combination with laser, radiation pressure and laser ablation slightly improved Corticosteroids at 4-6 weeks intervals (recurrence 10-30%) Targeted therapies Under development Need for further understanding of how keloids develop KELOIDS IN RTS Keloids in RubinsteinTaybi syndrome: a clinical study A.L. van de Kar, G. Houge, A.C. Shaw, D. de Jong, M.J. van Belzen, D.J.M. Peters and R.C.M. Hennekam British Journal of Dermatology 2014 KELOIDS IN RTS 24% of RTS patients develop keloids 50/50 men/women Mean age first keloid 11 .9 yrs Ethnicity: predominantly white (Dutch and UK patients) (Hardly) no family history Patients with CREBBP mutations increased risk Severe itching (89%) Dif ferences in behaviour (37%) Pain, restriction in movement, infection, sleep problems Van de Kar et al. 2014 KELOIDS IN RTS 22/27 patients more than one keloid Most located in the sternal area and the shoulder Treatment limited value Steroid injection (4) Lotion (5) Laser therapy (1) Pressure therapy (1) Copied from Van de Kar et al. 2014 RISK OF DISEASE AND HEREDITARY FACTORS Economy Relationships Complex diseases Luck Excercise Environment DNA kdaljf Health Example: keloids MONOGENIC DISEASES CAN SOMETIMES BE USED AS MODELS FOR COMPLEX DISEASES DE NOVO MUTATIONS 3 billion base pairs 20.000 genes We all have some gene variants not inherited from our parents This is the case in most RTS patients HEREDITARY CONDITIONS WITH KELOID FORMATION USED AS A MODEL TO UNDERSTAND HOW KELOID FORMATION OCCURS (GENE 1 -3 UNPUBLISHED) Gene 1 Gene 2 KELOID formation RTS Gene 3 RTS biobank: Raoul CM Hennekam & Dorien JM Peters EXAMINE GENE EXPRESSION IN CULTURED RTS SKIN CELLS 2 CREBBP 1 EP300 1 unknown Healthy skin Border Keloid Compared to patients with mutations in Gene 1 and 2 GENE 1-3 Currently examining Gene 1 -3 and how this af fects protein function. Compare to gene expression dataset SUMMARY Keloid is a frequent problem for RTS patients Itching particularly problematic Treatment dif ficult We use RTS and 3 other hereditary conditions with keloid formation to try and unravel how keloid formation occur This is an important step to try to improve treatment KELOID TEAM Raoul CM Hennekam Dorien JM Peters Gunnar Houge Ove Bruland Eyvind Rødahl Hans Dauwerse Linda Xu Cecilie Bredrup