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Early Hearing Detection
and Intervention
…Promoting communication from birth
Sensorineural Function of the Cochlea
“With over a million essential moving
parts, the auditory receptor organ, or
cochlea, is the most complex
mechanical apparatus in the human
body.” (Hudspeth 1985)
Causes of Prelingual Hearing Loss
50% Genetic
50% Environmental
30% Syndromic
(>400)
24% CMV intrauterine
infection
70% nonsyndromic
(usually sensorineural)
Other infections
Rubella
Bacterial Meningitis
Toxoplasmosis
NICU-related
hypoxia
Rh incompatibility
ototoxic medications
low birth weight
22% autosomal dominant (29 loci)
77% autosomal recessive (30 loci)
1% X-linked (8 loci)
<1% mitochondrial (2 loci)
Causes of Prelingual Hearing Loss
Recent Genetic Research Designs:
Include people diagnosed with hearing
loss in childhood
Exclude children with syndromes
Exclude children with known risk factors
Prelingual Hearing Loss
50% Genetic
50% Environmental
30% Syndromic
(>400)
24% CMV intrauterine
infection
70% nonsyndromic
(usually sensorineural)
Other infections
Rubella
Bacterial Meningitis
Toxoplasmosis
NICU-related
hypoxia
Rh incompatibility
ototoxic medications
low birth weight
22% autosomal dominant (29 loci)
77% autosomal recessive (30 loci)
1% X-linked (8 loci)
<1% mitochondrial (2 loci)
Nonsyndromic Hearing Loss
Unknown:
K+ channel:
Connexins:
Cytoskeleton:
Extracellular Matrix:
Transcription Factors:
Mitochondrial:
DFNA5
KCNQ4
GJB2
(Connexin 26)
GJB3
GJB6
MYO7A
MYO15
DIAPH1
OTOF
TECTA
COCH
POU3F4
POU4F3
12S rRNA
tRNASer
Nonsyndromic Hearing Loss
Single genes
(connexin 26)
Gene + environment
(mitochondrial + ototoxic medications)
Gene + gene
(mitochondrial plus other)
Other gene-environment interactions?
Causes of Prelingual Hearing Loss
50% Genetic
50% Environmental
30% Syndromic
(>400)
24% CMV intrauterine
infection
70% nonsyndromic
(usually sensorineural)
Other infections
Rubella
Bacterial Meningitis
Toxoplasmosis
NICU-related
hypoxia
Rh incompatibility
ototoxic medications
low birth weight
22% autosomal dominant (29 loci)
77% autosomal recessive (30 loci)
1% X-linked (8 loci)
<1% mitochondrial (2 loci)
Syndromic Hearing Loss
Alport
Charcot-Marie-Tooth
Goldenhar
Jervell and Lange-Nielsen
Mitochondrial disorders
Neurofibromatosis
Norrie Disease
Pendred
Treacher Collins
Stickler
Usher
Waardenburg
Vohwinkle
Risk Factors for Hearing Loss
In utero infection
Neonatal bacterial meningitis
CMV, Herpes, HIV, Rubella, Syphilis
In utero exposure to ototoxic drugs
Aminoglycosides, Alcohol, Cocaine
Intrauterine growth restriction
Premature birth
Low birthweight
Hyperbilirubinemia
Mechanical ventilation
Head trauma
Recurrent or persistent otitis
media
Treatment with
aminoglycoside antibiotics
Family History , Genetics
Causes of Hearing Loss
Do other genetic and/or
environmental factors modify
expression of hearing loss in
syndromes?
Gene-environment interactions?
Level 2 Research –
Etiology of Hearing Loss in Infants and Young Children
Cases:
Infants with a permanent hearing loss
identified through the universal newborn
hearing screen;
Children who passed the screen at birth
but are diagnosed with hearing loss before
the age of 3
Level 2 Research –
Etiology of Hearing Loss in Infants and Young Children
Methods:
collect information on known factors
and family history
clinical evaluation
DNA analysis of GJB2 (Connexin 26),
A1555G and A7445G (mitochondrial
genes)
Level 2 Research –
Etiology of Hearing Loss in Infants and Young Children
GA
HI
RI
UT
Estimated
Eligible
Participants
Per Year
30
25
30
90
Estimated
Total
Participants
Over 3 years
77
64
77
175
Estimated Total Participants = 448
Based on estimated 80% participation
Level 2 Research –
Etiology of Hearing Loss in Infants and Young Children
Analyses:
Description of factors associated with
hearing loss in infants and young children
Association of specific genes with hearing
loss in infants and young children
Level 2 Research –
Etiology of Hearing Loss in Infants and Young Children
Analyses:
Interaction between genes and
environment that cause hearing loss
Gene-gene interactions that cause
hearing loss
Early Hearing Detection
and Intervention
…Promoting communication from birth