Other symptoms

1. Other symptoms Jean Y Tang MD PhD Professor of Dermatology

2. Disclosures Founder, Board of Directors, Stockholder, Consultant: PellePharm Co-inventor, topical itraconazole gel for BCC I will discuss the off-label use of vismodegib

3. Overview • Non-skin symptoms of Gorlin Syndrome • Ovarian fibromas/cysts • Scoliosis • Emotional life and depression • QOL scores: impact on future drugs and insurance payment • Why GS Alliance Matters

4. Results from Registry: Other Skin, Brain, Ovarian Symptoms 58% 6% 13% 23% 4% 3%

5. Results: Other Skin, Brain, Ovarian Symptoms 58% 6% 13% 23% 4% 3%

6. Current protocol for care management (pediatric) • Baseline MRI of brain; repeat yearly (if asymptomatic) until age 8 yr, then discontinue • Baseline dermatologic examination; repeat yearly until first BCC develops and then every 6 months (or more frequently as needed) throughout life • Baseline Digital Panorex of jaw as soon as tolerated and then yearly until the first jaw cyst develops. Repeat every 6 months until no jaw cysts for 2 years or until age 21 yr • Pelvic ultrasonography in girls at menarche (or earlier if symptomatic). Repeat if symptomatic • Molecular diagnosis (if desired) for patients with family history and known mutation • Baseline scoliosis assessment at one year of age and then every 6 months for progression if present • Routine developmental screening and referral for all children who do not meet developmental milestones • Baseline cardiac ultrasound. Repeat if symptomatic • Annual vision, hearing, and speech screening through school age • Baseline ophthalmology evaluation. Repeat if symptomatic • Baseline psychological evaluation. Follow-up as needed • Minimize radiation exposure, maximize protection

7. Current protocol for care management (adults) • Baseline MRI of brain (if not done at age 8 yr or later). Repeat as needed if symptomatic • Dermatologic examination every 4 mo (or more frequently if new lesions present at each examination). More frequent skin evaluation if new lesions appear at each visit • Digital Panorex of jaw annually. Repeat as needed if symptomatic • Prenatal or preconception counseling if desired. Ob/gyn evaluation annually. Pelvic ultrasound at baseline and if symptomatic • Medical/clinical genetics counseling   • Psychological evaluation as needed • Neurology evaluation if prior diagnosis of medulloblastoma • Annual nutritional assessment of vitamin A, B, C, D • Minimize ionizing radiation, maximize sun protection

8. Quality of Life: Emotional, Social and Physical Impacts of Gorlin Syndrome

10. Your participation counts: Results from the GS Alliance (BCCNS network)

11. You are not alone: Gorlin syndrome patients have more worry and depression

12. You are not alone: GS affects your emotional and social life

14. Over 50% of GS patients are clinically depressed

15. Emotional life is impacted no matter how many BCCs you have Median: 145 BCCS # Lifetime BCCs Participant ID *Average Current Age: 40.4 Years

16. GS impacts Skindex score: surveys count

17. Guided by patient and family questions • Listen • Connect: meetings, Facebook, whatever forum works for you • Make your voice count • Participate in studies and trials

18. Other symptoms Thank you Jean Y Tang MD PhD Professor of Dermatology tangy@stanford.edu