Transcript Hearing Loss & Genetics

What Is In Your Genes?
Anna Frangulov, B.S. Research Coordinator
Children’s Hospital Boston
Why Hearing Loss is
So Common?
Structure of the Ear
Hair Cell the Cochlea “snail”
Sound wave
Extensions
Hair Cell
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 Passed On
(Inherited)?
 Recessive ~80%
 Dominant ~15%
 X-Linked ~2%
 Mitochondrial >2%
Dominant Inheritance
Mutation
“error"
Hearing
Loss
Hearing Loss Hearing Loss
Hearing
Hearing
Hearing
Point #1
The risk rate is for every child
Carrier
Mutation
“error"
Hearing
How a Recessive Mutation is
Passed?
Carrier –No Hearing Loss
Affected Child—
Hearing Loss
Carrier –No Hearing Loss
Recessive Inheritance
Hearing
Hearing Loss
Hearing
Hearing
Hearing
Hearing
Point #2
Most children with genetic cause of hearing loss
are born to parents with normal hearing
Sex Chromosomes
Hearing Loss
Hearing
X-Linked Inheritance
HL
Mitochondrial Inheritance
Hearing Loss
Hearing Loss
Hearing Loss Hearing Loss
Hearing Loss
Dominant Inheritance
Hearing Loss
Every child has 50%
Recessive Inheritance
Hearing “Carrier”
Hearing “Carrier”
Every child has 25%
X-Linked
Mitochondrial
Mutation is on X
chromosome
Mother
All males have 50%
All children w/HL
HOW? WHO? WHY?
HOW
Do We Know if HL is Genetic?
WHO
Should Have a Genetic Test?
Everybody with Sensorineural HL
Also 2 Mutations in
Cx26!!

Case A: Syphilis

Case B: CMV

Case C: Prematurity

Case D: High bilirubin level
Point #3
Even if you know your cause for hearing loss, you
may also have an underlying genetic cause
WHY
Should We Have a Genetic Test??
Benefits
 a definite cause
 family members realize that they are
carriers & determine risk factors for future
children
 helps to find appropriate treatment/
management
Limitations
 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
1.Talk to knowledgeable
professional
 Primary Care/ Pediatrician
 ENT
 Audiologist
 Clinical Geneticist
 Genetic Counselor
 Clinical Molecular Geneticist
Things to Consider
2. What tests are done?
Cx26
Cx30
Mitochondrial Tests
Pendred
3. Cost
UNDERSTANDING
TEST RESULTS
(example Cx26)
What Does the Result Mean?
 Two Mutations are Found
~18%
 Mutations w/Unknown
 No Mutations are Found
~70%
 One Mutation is Found
Significance
??
~1%
~10%
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
Two GeneChips are available right now:
Deafness GeneChip (Rehm Study):
MYO7A, OTOF, MYO6, USH1C,
PRES, TMPRSS3, TMIE, GJB2
Deafness GeneChip (Greinwald Study):
MYO7A, OTOF, CHDH23, KCNE1, KCNQ1,
PDS, GJB6, GJB2
Things to Remember
 Most children with HL are born to
parents with normal hearing
 The risks rates is for every child
 If you have other cause for hearing
loss you may also have an
underlying genetic cause
 A negative genetic test result =
inconclusive
Questions?
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 Materials
http://hearing.harvard.edu
Also in Spanish!
Helpful Information
 Genetic Counselor - Rebecca Madore call 617-355-4534 to set an
appointment or email [email protected]
 Department of Clinical Genetics – To make appointment with Clinical
Geneticist call 617-355-6394.
 National Society of Genetic Counselors (NSGC)
www.nsgc.org
 Help us evaluate educational material
 Research Study Participation & Booklets Orders:
Anna Frangulov
617-515-2962 or [email protected]