Presented by: Christine Shaver, MD and Herbert Allen, MD.
Drexel University College of Medicine
May 16, 2016
Gorlin syndrome, also known as Basal Cell Nevus syndrome, is a rare genodermatosis with an incidence of 1 in 19,000 to 256,000 people. The condition results from a mutation in the PTCH1 gene found on chromosome nine, and while it is generally inherited in an autosomal dominant manner, up to 50% of patients represent de novo mutations. The PTCH1 gene functions as a tumor suppressor and encodes the sonic hedgehog transmembrane receptor protein that interacts with signaling effectors to control cell fate, patterning, and growth. When PTCH1 is mutated, the PTCH protein can no longer inhibit Smoothened (SMO), which is then free to activate the signaling cascade and promote tumor formation.
The syndrome may present at birth with bossing and skeletal abnormalities, or it may present later in childhood with the development of jaw cysts and basal cell carcinomas. The first observed basal cell carcinomas present at a mean age of 23 years in Caucasians and 21 years in African-Americans, and tumors can vary in number from one to greater than one-thousand. Affected patients may also have palmoplantar pits, milia, hamartomas, and epidermoid cysts.
Additionally, Gorlin syndrome may involve other parts of the body aside from the skin. Nearly three-quarters of patients will have odontogenic keratocysts in the molar or premolar areas of the maxilla. Skeletal survey may reveal bifid ribs, vertebral fusion, kyphoscoliosis, or carpal bone abnormalities. Evaluation of the head and neck may reveal macrocephaly, frontal bossing, hypertelorism, and overall coarse facial features. Ocular examination may show cataracts, colobomas, and strabismus. Calcification of the falx cerebri and agenesis of the corpus collusum may be seen on MRI. Five to ten percent of patients develop medulloblastoma, often at an age less than two years-old, which may lead to premature death.
The mainstay for management of these patients is through regular skin examination with emphasis on photoprotection and avoidance of radiation exposure. Basal cell carcinomas that are detected may require surgery or an alternative treatment such as cryotherapy, photodynamic therapy, 5-fluorouracil, or imiquimod cream. Some patients may benefit from long-term treatment with oral retinoids, such as isotretinoin or acitretin, while advanced basal cell carcinomas may improve with vismodegib. Appropriate referral to a dentist, orthopedist, neurologist, and ophthalmologist are advisable based on history and physical examination.
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