The syndrome is caused by gene defects that regulate growth and differentiation; mutations in the PTCH gene impair the PTCH protein inhibition of SMOOTHENED (SMO), a transmembrane protein. SMOs active signaling contributes to tumor formation … Clues to the diagnosis in early life include a family history, frontal bossing, and hypertelorism … Cleft lip and palate may be associated … BCCs begin in early childhood, and are often small, banal appearing monomorphic, brown, smooth dome shaped papules, very acrochordon-like, and not looking like typical adult BCC’s at all … Learning difficulties are common … A pediatric dentist should be part of the care team … Photoprotection is important, and should include sunprotective garments, hats, and broad-spectrum sunscreens … X-rays and radiotherapy should be avoided … Consider topical imiquimod as a treatment option … LE

XP is caused by gene mutations responsible for the repair of UV-induced DNA damage, which involves recognition of damaged DNA, unwinding of the DNA by helicase, and incision and removal of injured DNA strands by endonucleases; each step has mutations associated with one or several complementation groups … Photosensitivity in infants can show up as crying on sun exposure … Families shouldn’t make their life adjustments alone; the XP support group and website www.xps.org, is invaluable in keeping “state of the art” with XP care … Sunprotective garments or UV suits, window tinting, and UV meters are important parts of care, along with constant broad-spectrum sunscreen, to be worn inside and out … Children may be tutored at home, although we have been able to accommodate classrooms with UV filters and set-up special programs … Consider developmental delay, and refer early for evaluation and management … Vigilant cancer screening is crucial, and serial photography is very useful to track changing skin lesions … “Camp Sundown” is a must—it is a camp dedicated to sun-sensitive children and their families … LE

Ophthalmic sebaceous tumors may be a presenting sign … Sebaceous adenoma or carcinoma should prompt a trip to an internist for a screening evaluation, looking for visceral malignancies … Sebaceous hyperplasia and sebaceous epitheliomas arising witin nevus sebaceous of Jadassohn are not part of the syndrome … The associated visceral malignancies may be indolent, and detection can lead to prolonged survival … Both hereditary nonpolyposis colorectal cancer and Muir-Torre syndrome are caused by inherited DNA mismatch repair defect … Mutations in the MSH2 gene located on 2p are commonly implicated, while mutations in the MSH1 gene located on 3p, can also cause the syndrome … LE

Dyskeratosis congenita is caused by inherited defects in the telomerase complex … Autosomal dominant dyskeratosis congenita is associated with mutations in the RNA component of telomerase, hTERC, while X-linked dyskeratosis congenita is caused by mutations in the gene encoding dyskerin, a protein implicated in both telomerase function and ribosomal RNA processing … X-linked dyskeratosis congenita is clearly the most common … X-linked recessive and autosomal recessive cases have a high incidence of nail dystrophy, skin changes and leukoplakia, with earlier presentation (median is approximately 15 years) … Autosomal dominant cases are usually milder, and may present later (median age at diagnosis, 28 years) … Some patients may be thought to have twenty-nail dystrophy; pigmentary and mucosal changes are sufficient to make the differentiation … Bone marrow dysfunction can be the first manifestation … Mucosal surfaces should be followed carefully with liberal biopsies of any worrisome changes … Hematopoietic stem cell transplantation is the standard treatment of bone marrow complications; nonmyeloablative conditioning regimens may be more successful. LE