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

Why Hearing Loss is So Common?

Structure of the Ear

Inside the Cochlea “snail” Sound wave Hair Cells Nerve

Structure of the Ear Conductive HL Sensorineural HL

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

How Genetic HL occurs?

Chromosomes in Nucleus 23 Pairs of Chromosomes MOM DAD

One Chromosome Pair Genes “instruction manual”

Genes

Chromosome Pair Genes Mutation “error”

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

Dominant Inheritance Mutation “error"

Carrier Mutation “error"

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

Recessive Inheritance

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

HOW? WHO? WHY?

HOW Do We Know If HL is Genetic?

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

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

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

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

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

UNDERSTANDING TEST RESULTS (example Cx26)

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

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

Future in Genetics and HL More Genetic Tests GeneChip Technology

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

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

Helpful Information Genetic Counselor - Rebecca Madore call 617-335-4534 to set an appointment or email 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 Research Study Participation & Booklets Orders: Anna Frangulov 617-515-2962 or anna.frangulov@childrens.harvard.edu