Download Cecilie Bredrup - Rubinstein – Taybi Syndrome Support Group

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
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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
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Raoul CM Hennekam
Dorien JM Peters
Gunnar Houge
Ove Bruland
Eyvind Rødahl
Hans Dauwerse
Linda Xu
Cecilie Bredrup