Session Objectives:

  1. Educate the FDA staff on the complex issues of Gorlin syndrome (GS), both related to the basal cell carcinoma’s (BCCs) and the variety of physical manifestations and body systems affected. 
  2. Educate the FDA staff on the serious impacts of GS disease manifestations on patients, the effects on quality of life, the currently available treatments, the tremendous unmet medical need, and preferences for treatments and outcomes.
  3. Review goals for future interactions with the FDA to further advance understanding and pave the way for continued development of new treatments leading to improved quality and quantity of life of those with GS, and ultimately a cure.  

Summary of Topics Discussed:

  1. Gorlin syndrome is an autosomal dominant rare genetic disorder affecting  1 in 27,000 to 31,000 individuals.
    1. Affected individuals may have over 100 manifestations in every organ system. 
    1. The most common manifestations are pits on the palms and soles of the feet, basal cell carcinomas (BCCs), and odontogenic keratocysts (jaw cysts).
    1. Patients may develop thousands of BCCs in their lifetime in sun exposed and nonsun exposed areas starting as early as the toddler years. The extreme number of BCCs are the most burdensome manifestation that the majority of affected individuals experience. Current treatments include topical creams (5-FU, Aldara, retinoids), cryotherapy, laser therapy, curettage, photodynamic therapy (PDT) and most frequently, disfiguring surgery and Moh’s procedures. Oral medications (hedgehog inhibitors) available to adults only are effective but the side effects are intolerable to many. There is a tremendous unmet need for more and better treatment options.
    1. Dr. Erv Epstein, Dermatologist & medical expert spoke on Gorlin syndrome and his experience treating these patients for half a century. He noted a survey done years ago where 100 affected individuals had surgery for over 20,000 BCCs. 
    1. The odontogenic keratocysts (OKCs) have a 30-60% recurrence rate and can result in the loss of permanent teeth and bone (mandible & maxilla). Even with aggressive surgical treatment, recurrence of these cysts often occurs creating a large unmet medical need. 
    1. In a recent global survey of affected individuals and caregivers, it was noted that in the past 12 months, on average, 24.8 days were lost from work and school so that patients could  go to medical appointments and undergo treatments including surgery, and take time off for post-surgical recovery.
    1. In advance of the Listening Session, the FDA was provided with two articles from medical literature on Gorlin syndrome.

  1. Over 35 manifestations were cited as symptomatic issues by presenters, including BCCs, OKCs, medulloblastomas, cardiac and ovarian fibromas, macrocephaly, hydrocephalus, meningioma, cranial synostosis, cleft lip and / or palate, kidney malformation, fetal rhabdomyoma, malformed bones, scoliosis, strabismus, glaucoma. 
    1. Gorlin syndrome may affect every bodily system which contributes to the overwhelming disease burden. Themes of the presenters included the need to “always prepare for what is next” and the following conclusion which powerfully represents the sentiment of many.

“In my mind, I see my daughter’s joyful, open face transformed into one with shining scars sprinkled like leopard spots, her nose and eyelids twisted and torqued by scar tissue. The ache of knowing a future I cannot shield her from is deep and penetrating. It comes with a morbid assurance of constancy: There will never be a time when she won’t have to worry about cancer, when she can pause the march of cuts across her body. How do I prepare her for that? My breath is stolen by my own impotence. She is already in the mouth of the tiger. The bite is coming. And there will be many.                 

I will soothe my child in an embrace for as long as she will let me, but she doesn’t just need a mother to hold her. She needs something that can sedate the disease that has its jaws locked on her.”


  1. The unmet needs and burdens of the Gorlin syndrome community are tremendous and include the need for:
  1. More treatment options for the BCCs that result in less scarring and permanent disfiguration, less pain, less impact on self-image, fewer or no side effects, and take less time away from work / school / life.
    1. Greater health care provider knowledge of Gorlin syndrome which will lead to earlier diagnosis potentially lessening harmful exposure to ionizing radiation and sunlight.
    1. More treatments for the OKCs that will reduce their 30-60% recurrence rate.
  • The Gorlin Syndrome Alliance plans to conduct an Externally-Led Patient Focused Drug Development Meeting in 2021. This meeting will further enhance the FDA’s knowledge and understanding of the impacts of living with Gorlin syndrome and will collect systematic input from patients and caregivers that can be used in future benefit/risk determinations when reviewing new treatments.

Patients Represented

Patient and caregiver perspectives were submitted representing fifteen affected individuals. Four patients presented live statements on seven affected individuals; five patients’ stories were presented anonymously representing another eight.

Partner Organization

Hyman, Phelps & McNamara, P.C.

FDA Divisions Represented

FDA Attendees:

Office of the Commissioner (OC) (5 offices)

  • Patient Affairs Staff (organizer)
    • Office of Clinical Policy & Programs
    • Office of Combination Products
    • Office of Orphan Products Development
    • Oncology Center of Excellence

Center for Biologics Evaluation and Research (CBER) (2 offices)

  • Office of the Director
    • Office of Tissues and Advanced Therapies, Division of Clinical Evaluation and Pharmacology/Toxicology/Oncology Branch

Center for Drug Evaluation and Research (CDER) (8 offices)

  • Office of New Drugs
    • Office of the Center Director
    • Office of the Center Director/Professional Affairs and Stakeholder Engagement
    • Office of New Drugs/Office of Rare Diseases, Pediatrics, Urologic and

Reproductive Medicine/ Division of Rare Diseases and Medical Genetics 

  • Office of New Drugs/ Office of Oncologic Diseases/Division of Ophthalmology II
    • Office of New Drugs/ Office of Oncologic Diseases/Division of Ophthalmology III
    • Office of Translational Sciences/Office of Biostatistics/ Division of Biometrics III
    • Office of New Drugs/Office of Immunology and Inflammation/Division of Dermatology and Dentistry  

Non-FDA Attendees:

  • Reagan Udall Foundation


Discussions in FDA Rare Disease Listening Sessions are informal. All opinions, recommendations, and proposals are unofficial and nonbinding on FDA and all other participants. This report reflects the Gorlin Syndrome Alliance’s account of the perspectives of the patients, caregivers, and medical expert who participated in the Rare Disease Listening Session with the FDA. To the extent possible, the terms used in this summary to describe specific manifestations of Gorlin syndrome, health effects and impacts, and treatment experiences, reflect those of the participants and the individuals they may represent. This report is not meant to be representative of the views and experiences of the entire Gorlin syndrome patient population or any specific group of individuals or entities. There may be experiences that are not mentioned in this report.