Hearing Loss & Genetics:Hearing Loss & Genetics:

Understanding the BasicsUnderstanding the Basics

Anna Frangulov, B.S. Research CoordinatorAnna Frangulov, B.S. Research Coordinator

Children’s Hospital BostonChildren’s Hospital Boston

Why Hearing Loss is Why Hearing Loss is So Common?So Common?

Structure of the EarStructure of the Ear

Sound wave

Inside the Cochlea “snail”

Hair Cells

Nerve

Structure of the EarStructure of the Ear

Conductive HL Sensorineural HL

Genetic

• Infections

• Drug-Related

• Structural

What Causes Hearing Loss?

• Unknown

• Traumas/ Exposures

Non-Genetic

How Genetic HL occurs?How Genetic HL occurs?

Chromosomes in NucleusChromosomes in Nucleus

23 Pairs of Chromosomes

MOM DAD

One Chromosome PairOne Chromosome Pair

Genes“instruction manual”

Genes

Chromosome PairChromosome Pair

Genes

Mutation“error”

How Is Mutation Inherited?How Is Mutation Inherited?

Dominant Dominant ~15%~15% Recessive Recessive ~80%~80% X-Linked X-Linked ~2%~2% Mitochondrial Mitochondrial >2%>2%

Dominant Inheritance Dominant Inheritance

Mutation“error"

CarrierCarrier

Mutation“error"

How a Recessive Mutation is How a Recessive Mutation is Passed?Passed?

Carrier –No Hearing Loss Carrier –No Hearing Loss

Affected Child—Hearing Loss

Recessive Inheritance Recessive Inheritance

If a parent has a dominant mutation, EACH of their children has a 50% chance of having hearing loss

Dominant InheritanceDominant Inheritance Recessive InheritanceRecessive Inheritance

90% of all children w/HL have normal hearing parents!

Parent w/HL Parent w/o HLParent w/o HL

Child w/HL

Child w/ HL

If two parents have a recessivemutation, EACH of their children has a 25% chance of having hearing loss

HOW? WHO? WHY?HOW? WHO? WHY?

HOWHOW

Do We Know If HL is Genetic? Do We Know If HL is Genetic?

WHOWHO Should Have a Genetic Test?Should Have a Genetic Test?

Case A: SyphilisCase A: Syphilis Case B: CMVCase B: CMV Case C: PrematurityCase C: Prematurity Case D: High bilirubin level Case D: High bilirubin level

Everybody with Sensorineural HLEverybody with Sensorineural HL

Also 2 Mutations in Also 2 Mutations in Cx26!!Cx26!!

WHYWHY Should We Have a Genetic Test??Should We Have a Genetic Test??

Benefits for Genetic TestingBenefits for Genetic Testing a definite causea definite cause family members realize that they are family members realize that they are

carriers & determine risk factors for future carriers & determine risk factors for future childrenchildren

helps to find appropriate treatment/ helps to find appropriate treatment/ managementmanagement

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

have HLhave HL

Things to ConsiderThings to Consider

1.1. Talk to knowledgeable professionalTalk to knowledgeable professional

Primary Care/ Pediatrician

ENT

Audiologist

Clinical GeneticistClinical Geneticist

Genetic CounselorGenetic Counselor

Clinical Molecular GeneticistClinical Molecular Geneticist

Things to ConsiderThings to Consider

2. What tests are done?2. What tests are done?

Cx26Cx26 Cx30Cx30 Mitochondrial TestsMitochondrial Tests PendredPendred

3. Cost3. Cost

UNDERSTANDING UNDERSTANDING TEST RESULTSTEST RESULTS

(example Cx26)(example Cx26)

What Does the Result Mean?What Does the Result Mean?

Two Mutations are FoundTwo Mutations are Found No Mutations are FoundNo Mutations are Found

Mutations w/Unknown Mutations w/Unknown Significance Significance

One Mutation is FoundOne Mutation is Found

??~10%

~70%~18%

~1%

One Mutation FoundOne Mutation Found

Mutation unrelated to deafnessMutation unrelated to deafness Test did not find 2Test did not find 2ndnd mutation mutation Dominant mutationDominant mutation There may be a mutation in another geneThere may be a mutation in another gene

Future in Genetics and HLFuture in Genetics and HL

More Genetic Tests More Genetic Tests

GeneChip TechnologyGeneChip Technology

Research StudiesResearch Studies Connexin 26 Study-Connexin 26 Study- individuals with Cx26 mutations individuals with Cx26 mutations

Genetic Testing and Counseling StudyGenetic Testing and Counseling Study - - If you or your If you or your child has had genetic testing for hearing loss and you child has had genetic testing for hearing loss and you are willing to fill out a questionnaireare willing to fill out a questionnaire

GeneChip Study - GeneChip Study - individuals with hearing loss who and individuals with hearing loss who and parents with normal hearing parents with normal hearing

Novel Gene Discovery StudyNovel Gene Discovery Study - - five or more family five or more family members with hearing loss members with hearing loss

Now also in Spanish!

Educational Material

http://hearing.harvard.edu

Helpful InformationHelpful Information

Genetic Counselor -Genetic Counselor - Rebecca Madore call 617-335-4534 Rebecca Madore call 617-335-4534 to set an appointment or email to set an appointment or email rmadore@partners.org

Department of Clinical GeneticsDepartment of Clinical Genetics – To make appointment – To make appointment with Clinical Geneticist call 617-355-6394.with Clinical Geneticist call 617-355-6394.

National Society of Genetic Counselors (NSGC)National Society of Genetic Counselors (NSGC) www.nsgc.org

Research Study Participation & Booklets Orders: Research Study Participation & Booklets Orders: Anna Frangulov Anna Frangulov

617-515-2962 or anna.frangulov@childrens.harvard.edu617-515-2962 or anna.frangulov@childrens.harvard.edu