Tuberous Sclerosis

• Topical Rapamycin could be used to treat facial angiofibromas (“Adenoma Sebaceum”) (link) (Archives of Dermatology, 2010)

Neurofibromatosis (Recklinghausen’s Disease)

• Mast cells play an important role
• The c-Kit receptor on mast cells is stimulated by mediators that are liberated by Schwann cells
• The activation of mast cells then induces the liberation of maediators that lead to proliferation of Schwann cells and the subsequent tumor formation.

• Imatinib inhibits c-Kit activation and could therefore play a role

Basal Cell Carcinoma (BCC)

• In Gorlin’s Syndrome as well as sporadic BCCs, mutations of the PTCH (Patched) gene have been found.
• This mutations leads to the overactivity of the hedgehog pathway and subsequent carcinoma formation.

• Inhibition of this pathway through inhibition of SMO (Smoothened) is possible with oral and topical substances (LDE 225 is an example…)

Progeria

• Mutations of the LMNA gene have been found

• Inhibition of the nuclear activation is possible with inhibitors of farnexytransferase

Recessive Dystrophic Epidermolysis Bullosa (EB)

• deficiency of collagen VII is responsible for this condition.

• It has been shown that injection of collagen VII into the wounds can reverse this phenomenon
• When applied topically, it has been shown to accelerate wound healing in mice.

CHILD syndrome (Congenital Hemidysplasia with Ichtyosiform Lesions and Limb Defects)

• Proteolysis of HMG Co-A is dependant on cholesterol. A lack of this leads subsequently to an abnormal Stratum Corneum.

• Topical formulations containing 2% lovastatin and 2% cholesterol have been shown to show good clinical results (link)

Epidermolysis Bullosa Simplex (EBS)

• Symptoms are due to a mutation and functional absence of keratin 14 (K14)

• Addition of K16 can compensate for this loss.
• Sulforaphane in Broccoli Sporouts could compensate for this loss by supplying K16 and K17.

Contributors:

Dr Christophe HSU – dermatologist. Geneva, Switzerland

Source of Information: SY 22. Paller A. Update on Genetic Disorders. 2012 (06) – 9th Spring Symposium of the EADV (European Academy of Dermatology and Venerology) – Verona, Italiy (Italia)