Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Gorlin Syndrome

Gorlin syndrome is also known as nevoid basal cell carcinoma syndrome, but we’ll stick with Gorlin syndrome for now.

What is Gorlin Syndrome?

• A rare inherited disorder that can affect all systems of the body and makes affected individuals more susceptible to various forms of cancer especially basal cell skin cancer​
• Typically characterized by multiple basal cell skin cancers​
• Individuals with Gorlin Syndrome typically have characteristic features including skeletal abnormalities and jaw cysts​
• Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood
• The name Gorlin syndrome refers to researcher Robert J. Gorlin (1923–2006)​
• The severity of NBCCS can vary, and some individuals with mild forms can go undiagnosed, while others can have significant complications

How Do You Get It?

• Caused by mutations in the PTCH1 gene found on chromosome arm 9q​
• PTCH1 provides instructions for making a protein called patched-1, which functions as a receptor​
  • The PTCH1 gene is a tumor suppressor gene, which means it stops cells from proliferating too rapidly or in an uncontrolled way​
• Mutations in this gene prevent the production of patched-1 or lead to the production of an abnormal version of the receptor​
  • An altered or missing patched-1 receptor cannot effectively suppress cell growth and division
• Environmental exposure and other modifier genes may contribute to the variation in symptoms seen amongst patients

What Are The Symptoms?

• Major Features
  • Basal cell carcinomas​
    • Ranges from only a few spots to thousands of tiny lesions​
    • Patients have a 90% risk of developing BCC​
    • Do not usually spread to other areas of the body, but they can become aggressive and invade local tissue​
    • Most common on sun exposed areas of the skin​
    • If left untreated BCCs can cause disfigurement, especially if located on the face​
    • Usually develop between puberty and the mid-30s​
    • Approximately 10% of individuals, especially those with dark skin and limited sunlight exposure, do not develop any basal cell carcinomas
  • Keratocystic odontogenic tumors (benign jaw cysts)
    • Affected individuals usually develop multiple, recurrent cysts​
    • Are often aggressive, progressing to cause pain, fractures, loose teeth or displacement of developing permanent teeth​
    • If left untreated, they can potentially damage large portions of the jaw​
    • Often the first presenting sign in many individuals​​
  • Multiple palmar pits​
  • Increased calcium deposits in the head (usually asymptomatic)​
• Minor Features
  • Medulloblastoma (most common malignant brain tumor in childhood – developed by about 5%)​
  • Increased head size and large forehead​
  • Cleft lip or palate​
  • Extra fingers or toes​
  • Abnormal shape of the ribs or spinal bones​
  • Eye problems such as cataracts, small eyes, or tumors in the iris​
    • Widely spaced eyes
  • Fibromas, meaning benign fibrous tumors, of the ovaries or heart​
  • Abdominal cysts/cardiac fibromas/ovarian fibromas​
  • Tiny white bumps or cysts on skin
  • Coarse facial features

How Is It Treated?

• Treatment is based on the patient’s symptoms​
• Specialists that may be involved in treatment include:​
  • Pediatricians​
  • Dermatologists​
  • Oral surgeons​
  • Dentists​
  • Cardiologists​
  • Ophthalmologists​
  • Plastic surgeons​
• Treatment options include:​
  • Topical chemotherapy​
  • Surgery​
    • The main treatment for BCC in Gorlin Syndrome is surgery​
    • Due to the large number of tumors expected over a lifetime, surgical methods should be chosen keeping in mind the cure rate and scarring potential​
    • Reconstruction after tumor removal should take into account the likelihood of further BCCs in the vicinity and should be kept simple whenever possible​
    • Excision​
    • Mohs micrographic surgery​
  • Drug therapy​
    • Includes topical and oral chemotherapy agents, retinoids and interferon​
    • Odomzo (sonidegib)
      • Indicated for treatment of adult  patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy​
      • Oral signal pathway inhibitor​
      • First approved in July 2015​
    • Erivedge (vismodegib)
      • An oral targeted therapy indicated for  the treatment of adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation​
      • Not specifically FDA approved for Gorlin Syndrome, but many do fit the criteria for use due to their BCC​
      • First approved in 2012​
      • 21% of patients involved in the clinical research study for Erivedge had Gorlin Syndrome​
      • Taken once daily
    • Topical chemotherapy agents can be used so the patient can self-treat smaller lesions​
      • 5-fluorouracil​
      • Aldara –imiquimod 5% – FDA approved in 2004. Generics available​
  • Cryotherapy​
  • Electrodessication and curettage​
  • Photodynamic therapy​
    • A drug known as a photosensitizer is used along with a special type light to treat those with large lesions​
  • Laser vaporization

Where Can I Learn More???

• Check out our cornerstone on this disease here.