Congenital Hearing Loss Flashcards
What is the difference between Congenital, Familial and Genetic?
Congenital – trait present at birth
Familial – trait appears in more than one family member
Genetic – condition resulting from change or variation in genes
What are two ways to describe genetic traits?
Inherited
New mutation
What is the relationship between genetic and congenital?
Genetic is always congenital but congenital is not always genetic
Eg congenital Cyto Megalo Virus infection
What is the relationship between Congenital, Genetic, and late-onset?
Congenital and genetic disorders are present at birth but may not express themselves until later in life (late onset)
Estimates for congenital SNHL range from __________________ and congenital CHL hearing loss is ______________________
Estimates for congenital SNHL range from 1/500 to 1/2000
Congenital conductive hearing loss is much less common
Why do we need NBHS (New Born Hearing Screen)?
We want to diagnose kids before 6 months to have less impact on language development
What does the Study show?
Age of identification influences language development
Other reasons
Health (quality of life)
Economic (productive life)
Moral
What are the 2 common methods of NBHS?
Otoacoustic emissions (OAE)
Automated auditory brainstem response (AABR)
What are Otoacoustic emissions? (3)
- Normal cochlea produces low-intensity sounds (OAEs)
- Originates from outer hair cells as they expand and contract
- No behavioral response required
How do ABR work? (3)
Automated auditory brainstem response
- Parts of auditory brainstem function tested
- Evoked potential generated by click stimuli
- No behavioral response required
Who performs OAE and ABR?
Usually performed by audiology technicians
What are the reasons NBHS can be missed by babies?
- Home births
- Parental refusal
- Transferred/discharged prior to test
- Certain hospitals
What are NBHS caveats? (3)
- Universal screening must weigh risk vs benefits
Costs, anxiety caused by false +ve results - NBHS expanded to all of NS in 2006/2007
- Realistic aim is to screen >95% of newborns by age 3 months
What are the false positive rates of AABR and OAE?
AABR: 1-3% false +ve, more costly
OAE: 3-10% false +ve, less costly and quick
What is the protocol for both tests?
OAE
AABR
Both (2 stage testing)
Passing a NBHS does not guarantee: (2)
- That the infant has normal hearing
- That the infant will always have normal hearing
How can you pass a NBHS but have hearing loss? (6)
Hearing loss outside tested frequencies
Hearing loss is better than 35 dB screening threshold
Misinterpretation of results by the technician
Equipment malfunction
Hearing loss occurs after birth
Auditory neuropathy/dyssynchrony (OAE screens)
What happens after a failed NBHS?
-Testing repeated prior to leaving hospital
- Automatic referral to audiology within 2-3 months for diagnostic ABR
- Failed screen has many causes but some children will have normal hearing
What are the 5 main high-risk registers for hearing loss?
- Caregiver concern (hearing, speech, language, developmental delay)
- Family history of permanent childhood HL
- NICU > 5 days, assisted ventilation, ototoxic drugs, hyperbilirubinemia
- Prenatal infections (TORCH)
- Craniofacial anomalies
- Physical findings associated with HL syndrome
- Syndromes with associated HL
- Neurodegenerative disorders associated with HL (eg Charcot-Marie Tooth syndrome)
- Postnatal infections associated with HL (eg meningitis)
- Head trauma (eg basal skull fracture)
- Chemotherapy
- Recurrent or chronic OM (at least 3 months)
What is DNA?
- Deoxyribonucleic acid
- Composed of 4 bases
What are the base pairs of DNA?
- Adenine-Thymine
- Cytosine-Guanine
What are Genes?
Made up of DNA (1000 base pairs = 1 gene)
What are cells?
Smallest unit that can live on its own and that makes up all living organisms and the tissues of the body
What is Transcription and Translation?
Transcription
DNA -> RNA (ribonucleic acid)
Translation
RNA -> Protein
Protein-building blocks of life and biological function
Where do translation and transcription occur in the cells?
Translation - > Cytoplasm
Transcription -> Nucleus
What occurs in this picture?
The end product of the genetic code, the protein, will be abnormal because of mutation, bad replications or other anomalies in the codings of the pairs
Where is the energy produced in the cells?
in the Mitochondria which also contains DNA
What to we mean by genetic Hearing Loss?
- Chromosomal
- Autosomal
Involves genes on the 22 autosomal chromosomes - X-linked
Involves genes on the sex chromosomes - Mitochondrial
Only passed on by females (all mitochondria come from moms)
What is the percentage of types of HL?
Half genetic, one quarter Non-Genetic and one-quarter unknown
How many Chromosomes do we have?
46 chromosomes (23 pairs)
Short arm = p arm
Long arm = q arm
How many pairs of chromosomes are autosomes?
22 pairs of autosomes
How many pairs constitute the sex chromosomes?
1 pair of sex chromosomes (XY, XX)
What are the pairs of chromosomes of the Dad?
XY
What are the pairs of chromosomes of the MUM?
XX
What are autosomes?
Autosomes control the inheritance of all an organism’s characteristics except the sex-linked ones, which are controlled by the sex chromosomes.
What are the types of chromosomal abnormalities?
Extra or missing copies of chromosomes
0.4% of live births
Extra copy of chromosome (eg Trisomy 21, 18, 13)
Deleted copy of chromosome
Portions of chromosomes rearranged
Translocation, inversion
What are autosomal recessive?
Dad has one r abnormal gene ‘‘Carrier’’
Mom has one r abnormal gene ‘’ Carrier’’
Passes down to one child where the child by random chance the kid has rr chances of that happening is 1in4 25%
What is happening in this pedigree image?
Autosomal Recessive
Through generations circle female square is male
Black is affected
Can skip generations because carriers through generations
What are the chance of congenital HL through autosomal recessive?
- 35-40% of all congenital hearing loss
Up to 60% with unknown recessive genes - Most common pattern of genetic hearing loss
- For offspring to have disorder, both parents must be carriers of the gene
- 1 in 4 risk
What is autosomal Dominant?
Every generation is Carrier AND one Affected at least in each generation
What are the chances of autosomal dominant congenital hearing loss?
10% of all congenital hearing loss
Typically hearing impaired children of hearing impaired adults
Dominant genes may lack penetrance or show variable expressivity
1 in 2 risk
What is X-linked Recessive?
Transmitted on X chromosome
Fully expressed in males
Half will be affected
Females are carriers
Half will be carriers
Can X-Linked be dominant?
Yes, but rare.
Since females have 2 X chromosomes, they are more likely to suffer from dominant disorders
What is Mitochondrial Inheritance?
All mitochondria is inherited from the mother
Mitochondrial DNA (mDNA) is passed on without division or recombination
No father gene or mitosis
This has allowed tracing of mDNA in the human species
What is Mitochondria?
Site of cellular energy creation to sustain life and growth
What is the proportion of congenital hearing loss?
- Deafness affects 0.3%
- Congenital SNHL
50% genetic
25% environmental
25% sporadic
What is the proportion of 3 types of Genetic hearing loss?
Genetic hearing loss
75% autosomal recessive
20% autosomal dominant
5% x-linked or chromosomal
What is and important part of your initial assessment?
- Family history
- Any family members with hearing loss (childhood hearing impairment)
- Any family members with syndromes
- Any family members with special schooling
- Any family members with speech and language problems
How do we classify permanent childhood hearing loss due to a genetic cause?
- No associated abnormalities
- External ear abnormalities
- Musculoskeletal abnormalities
- Ocular abnormalities
- Integumentary system abnormalities
- Metabolic and renal disorders
- Nervous system disorders
- Cleft and craniofacial disorders
What is Genetic HL-No other features?
- Primary group which requires newborn hearing screen (other than high-risk register)
No obvious anomalies
Some can develop hearing loss later - Early identification leads to improved speech/language and educational opportunities
Give two Genetic Hearing Loss conditions with No Associated Abnormalities:
Connexin 26 and 30
Auditory neuropathy
________________
Gene mutations are named sequentially as they are found:
DFN ________________
A __________
B__________
- - ______________
#
(in order of discovery)
DFN (deafness gene)
A (dominant)
B (recessive)
- (X-linked)
#(in order of discovery)
What is DFNB1?
- First identified mutation of an autosomal recessive gene causing hearing loss
- Mutation in Connexin 26 protein
What is Connexin 26 (DFNB1)
- DFNB1 gene = gap junction beta-2 gene (GJB2)
- Found on chromosome 13
- Normally encodes Connexin 26 protein (or GJB2 protein)
- 6 Connexin proteins join to form a junction channel between cells
- DFNB1 = GJB2 = Connexin 26
Connexin 26 (DFNB1) accounts for
- Accounts for up to 50% of AR deafness
25% of genetic deafness
15% of all deafness - About 1/40 of NA population carry a mutation in Connexin 26 (1/6000 births affected)
- No vestibular abnormalities or radiographic abnormalities
What happens in terms of HL from Connexin 26 (DFNB1)
- Bilateral SNHL (usually > 40 dB)
- 40% have severe to profound HL
- 2% have mild HL
- Can be progressive
- Tends to do better than other types of deafness when fitted with cochlear implants
How can you test for Connexin 26?
- Testing
Can test for specific mutations but better to sequence the entire gene ($300/test)
What is Connexin 30? (3)
- Some people with SNHL have only 1 mutation in Connexin 26
- Many found to have a mutation in nearby gene (GJB6), which codes for Connexin 30
- Deafness may result in single Connexin 26
mutation AND single Connexin 30 mutation
What is Auditory Neuropathy?
- Aka auditory dyssynchrony
- Impairment of sound transmission from the inner ear to the brain
- Clinically mild to profound loss with worse-than-expected speech discrimination
- Hallmark of AN is an inconsistent response to sound
Outer hair cell function intact
Clinical definition of AN
Normal OAEs (cochlear microphonic)
Absent or severely abnormal ABRs
Familial form described with mutation in the Otoferlin gene (DFNB9)
AR
No syndromic features or radiologic abnormalities
Can be seen in Charcot-Marie-Tooth, Friedreich’s ataxia
Some benefit from cochlear implants
