1. Hearing Loss & Genetics: Understanding the Basics Anna Frangulov, B.S. Research Coordinator Children’s Hospital Boston

2. Why Hearing Loss is So Common?

3. Structure of the Ear

4. Sound wave Inside the Cochlea “snail” Hair Cells Nerve

5. Structure of the Ear Conductive HL Sensorineural HL

6. Genetic Infections Drug-Related Structural What Causes Hearing Loss? Unknown Traumas/ Exposures Non-Genetic

7. How Genetic HL occurs?

8. Chromosomes in Nucleus 23 Pairs of Chromosomes MOM DAD

9. One Chromosome Pair Genes “instruction manual”

10. Genes

11. Chromosome Pair Genes Mutation “error”

12. How Is Mutation Inherited?  Dominant ~15%  Recessive ~80%  X-Linked ~2%  Mitochondrial >2%

13. Dominant Inheritance Mutation “error"

14. Carrier Mutation “error"

15. How a Recessive Mutation is Passed? Carrier –No Hearing Loss Affected Child— Hearing Loss

16. Recessive Inheritance

17. If a parent has a dominant mutation, EACH of their children has a 50% chance of having hearing loss Dominant Inheritance Recessive Inheritance 90% of all children w/HL have normal hearing parents! Parent w/HL Parent w/o HL Child w/HL If two parents have a recessive mutation, EACH of their children has a 25% chance of having hearing loss

18. HOW? WHO? WHY?

19. HOW Do We Know If HL is Genetic?

21. WHO Should Have a Genetic Test?  Case A: Syphilis  Case B: CMV  Case C: Prematurity  Case D: High bilirubin level Everybody with Sensorineural HL Also 2 Mutations in Cx26!!

22. WHY Should We Have a Genetic Test?? Benefits for Genetic Testing  a definite cause  family members realize that they are carriers & determine risk factors for future children  helps to find appropriate treatment/ management

23. Limitations for Genetic Testing  does not necessarily find the answer  severity of HL may not be predicted  a person may have mutations, but not have HL

24. Things to Consider Things to Consider 1. Talk to knowledgeable professional  Primary Care/ Pediatrician  ENT  Audiologist Clinical Geneticist  Clinical Geneticist  Genetic Counselor  Clinical Molecular Geneticist

25. Things to Consider 2. What tests are done?  Cx26  Cx30  Mitochondrial Tests  Pendred 3. Cost

26. UNDERSTANDING TEST RESULTS (example Cx26)

27. What Does the Result Mean?  Two Mutations are Found  No Mutations are Found  Mutations w/Unknown Significance  One Mutation is Found ?? ~10% ~70% ~18% ~1%

28. One Mutation Found  Mutation unrelated to deafness  Test did not find 2 nd mutation  Dominant mutation  There may be a mutation in another gene

29. Future in Genetics and HL  More Genetic Tests GeneChip Technology

30. Research Studies  Connexin 26 Study- individuals with Cx26 mutations  Genetic Testing and Counseling Study - If you or your child has had genetic testing for hearing loss and you are willing to fill out a questionnaire  GeneChip Study - individuals with hearing loss who and parents with normal hearing  Novel Gene Discovery Study - five or more family members with hearing loss

31. Now also in Spanish! Educational Material http://hearing.harvard.edu

32. Helpful Information  Genetic Counselor - Rebecca Madore call 617-335-4534 to set an appointment or email rmadore@partners.org rmadore@partners.org  Department of Clinical Genetics – To make appointment with Clinical Geneticist call 617-355-6394.  National Society of Genetic Counselors (NSGC) www.nsgc.org www.nsgc.org  Research Study Participation & Booklets Orders: Anna Frangulov 617-515-2962 or anna.frangulov@childrens.harvard.edu 617-515-2962 or anna.frangulov@childrens.harvard.edu