Stickler Syndrome: A Family Story

1. Stickler Syndrome:A Family Story Paula Goldenberg, MD, MSW, MSCE 18th American Stickler Syndrome Conference Denver, Colorado July 12, 2014

2. Stickler Syndrome Basics • What causes Stickler Syndrome? • How Stickler Syndrome is passed down in families? • How can we modify our genetic risk? • What can we do to be in the best health possible?

3. Stickler Syndrome • Common (1:7500-1:9000 births) • Hereditary arthro-ophthalmopathy • Hearing loss is common in people with Stickler syndrome • Most common genetic association in patients with Pierre Robin sequence • Can affect many individuals in a family

5. Stickler SyndromeEye Findings • High Myopia • Retinal tears and detachment • Glaucoma • Cataracts http://epharmapedia.com Snead MP, Eye 2011;1389-1400

6. Joints • Joint laxity • Tall thin stature • Degenerative Arthropathy • Scoliosis http://www.qt.com.au Snead, MP; J Med Genet 36:353-359

7. Craniofacial • People with Stickler syndrome can resemble each other as well as their families • U-shaped cleft palate • Bifid uvula • Pierre-Robin Sequence http://ginoyton.com Antunes RB, J Plastic Recon AesthSurg 2012: 1029

8. Hearing Loss • 80% • Hypermobility • Conductive • Sensorineural • Mixed • Can worsen

9. Heart • Mitral valve prolapse

10. Stickler Syndrome Basics • What causes Stickler Syndrome? • How Stickler Syndrome is passed down in families? • How can we modify our genetic risk? • What can we do to be in the best health possible?

11. What causes Stickler syndrome? • Collagen: the gel, the cushion, and the girders • Compressible, Structural (crosslinking)

13. Where is collagen? • Joints • Bones • Cornea and vitreous (eye) • Skin • Intestines • Spinal disks • Dentin (teeth) • Muscle • Usually made by fibroblasts

14. Collagen: Many varieties! • Type I-Type XXVIII! • Each type has different properties and uses • 1,000 identified disease-causing mutations • Different types of collagen mutations can cause • Brittle Bone Disease (osteogenesisimperfecta) • Ehlers-Danlos Syndromes (many types) • Alport Syndrome (kidney failure and hearing loss) • Stickler Syndrome • And many, many others

15. Collagen 9A1

17. What does COL9A1 do? • Works with collagen 2 • In hyaline cartilage (articular joints)

19. Stickler Syndrome Basics • What causes Stickler Syndrome? • How Stickler Syndrome is passed down in families? • How can we modify our genetic risk? • What can we do to be in the best health possible?

20. Stickler SyndromeFamily Matters

21. Stickler Syndrome • Majority of patients have a parent with Stickler syndrome • If a patient is the first person with Stickler syndrome in the family we call this a de novo deletion

22. Chromosomes

26. Stickler Syndrome Inheritance • Two types • Autosomal Dominant • Autosomal Recessive

27. Autosomal Dominant InheritanceAffected Parent to Affected Child

28. Genes in Autosomal Dominant Stickler Syndrome • COL2A1: 80-90% Autosomal Dominant • Membranous vitreous anomaly with mild hearing loss • COL11A1: 10-20% Autosomal Dominant • Beaded vitreous anomaly with significant hearing loss • COL11A2: Rare Autosomal Dominant • “Non-ocular” Stickler Syndrome

29. Autosomal RecessiveParents are carriers and not affected

30. Genes in Autosomal Recessive Stickler Syndrome • COL9A1: Very Rare; Autosomal recessive • 3 families • COL9A2: Very Rare; Autosomal recessive • Two children in one family

31. Stickler Syndrome Basics • What causes Stickler Syndrome? • How Stickler Syndrome is passed down in families? • How can we modify our genetic risk? • What can we do to be in the best health possible?

32. Genetic Counseling: Low Tech • Autosomal dominant 50% risk with each pregnancy • Autosomal recessive 25% risk with each pregnancy • Level II ultrasound 18-20 weeks: micrognathia • For parents with all types of Stickler Syndrome • Amniocentesis or CVS • If familial mutation(s) known • Donor Egg • Donor Sperm • Adoption

33. Genetic Counseling: High Tech • If we know the gene mutation in the family

35. Stickler Syndrome Basics • What causes Stickler Syndrome? • How Stickler Syndrome is passed down in families? • How can we modify our genetic risk? • What can we do to be in the best health possible?

36. Unfortunately, this is not the answer

37. Rheumatology Orthopedics Ophthalmology Genetics Clinic Cardiology Craniofacial Audiology

38. Excellent Care: it takes a village! • Ophthalmology • Orthopedics • Rheumatology • Audiology • Craniofacial Team (Clefts, Pierre Robin) • Oral Maxillofacial Specialists • Cardiology • Genetics • Genetic Testing • Can be a quarterback for the team • Surveillance

39. The village continued… • Physical Therapy • Occupational Therapy • Physical Medicine and Rehabilitation • Vision Therapy • Hearing Aid Specialist • Social Work • Stickler Involved People • Stickler Syndrome Support Group (UK) • Facebook networks

40. Many Thanks To • Our patients and families affected by Stickler syndrome • Dr. Ruth Lieberfarb • Dr. David Sweetser • Dr. Joseph Thakuria

41. http://wendylhughes.blogspot.com/2012_06_01_archive.html