genetic testing and psychosocial/ ethical issues and genetic couseling

Question 1

what is assortative mating ?

Answer 1

Mating of people with the same phenotype resulting in more of the phenotype than expected by chance
ex. the deaf community?

Question 2

what is linguistic homogamy ?

Answer 2

Mating between individuals that have the same language such as “native” signers

Question 3

what is the founder effect ?

Answer 3

-Population derived from a small group of geographically or socially isolated, common with AR transmission
-As carriers of this disease have children and the new population starts to grow, the mutated gene becomes more prevalent
ex. ashkenazi jew

Question 4

what is population bottleneck?

Answer 4

-Reduction in population size, which enhances the effects of gene drift - random fluctuations in the numbers of gene variants in a population
For example:
-If the sample size of a population were to be reduced by natural causes such as a famine, or man made causes such as wars, the holocaust, or some form of ethnic cleansing
-Many genes would be lost forever but the remaining genes would appear to increase greatly due to the loss of population

Question 5

what is balanced polymorphism?

Answer 5

It is a process of natural selection; a system of genes in which two alleles are maintained in stable equilibrium because the heterozygote is more fit than either of the normal or affected homozygotes
ex. sickle cell anemia

Question 6

how to identify a HL with perinatal history

Answer 6

-Known factors causing hearing loss include
-Low birth weight
-Time spent in NICU (longer the time the greater the risk)
-Infections such as
-Sepsis, CMV, mumps, measles, rubella, and bacterial meningitis
-Use of ototoxic medication
-Hypoxia (or prolonged use of oxygen)

Question 7

what else could help identify an affected individual?

Answer 7

Record of speech and language milestones can establish whether the hearing loss was pre- or post-lingual
-DEAD INFANTS CAN STILL COO/BABBLE NATURALLY UP TO 6 MONTHS
History of poor motor development may indicate vestibular dysfunction

Question 8

how is family history help identify affected individuals

Answer 8

-Inquire about first- and second-degree relatives with hearing loss, especially if the loss occurred before age 30
-Consanguinity or common origin should increase the suspicion of hereditary hearing loss
-Progressive hearing loss
-If there are a number of family members with hearing loss, constructing a pedigree may define the mode of inheritance

Question 9

how can physical examination help identify affected individuals ?

Answer 9

-History or presence of pigmentary abnormalities may indicate Waardenburg syndrome
-Presence of branchial clefts/sinuses may indicate BOR syndrome
-Thyroid symptoms may indicate Pendred’s syndrome
-Visual and/or vestibular abnormalities may indicate Usher’s syndrome

Question 10

what are some audiological test to help us identify audiologic findings?

Answer 10

-OAE/ABR for young children
-Audiogram/behavioral assessment for older children
-Presence or absence of hearing loss in other family members should be documented

Question 11

how can lab test help us identify an affected individual

Answer 11

-The testing should be performed to exclude or confirm a specific suspected diagnosis
-Routine blood count and biochemical tests are generally unhelpful in establishing the cause for a hearing loss
-Urine analysis may be important for some conditions involving hematuria with/without proteinuria (e.g., Alport syndrome)

Question 12

how can endocrine function help identify with affected individuals ?

Answer 12

-Congenital/acquired neonatal thyroid hormone deficiency can result in profound intellectual disability often accompanied by deafness
-Early treatment can prevent severe hearing loss
-In Pendred syndrome, thyroid hormones T4, T3 and thyroid stimulating hormone (TSH), are generally normal
-Autoimmune work-up in sudden/progressive/fluctuating SNHL

Question 13

how can electrocardiograms help identify affected individuals ?

Answer 13

Calculation of the QT interval if family history of syncope or sudden infant death, which may be an indication of JLNS

Question 14

how can radiology help identify affected individuals?

Answer 14

-High-resolution CT scan of the temporal bones is important for children with a progressive SNHL and craniofacial anomalies
-It also is necessary to determine an enlarged vestibular aqueduct (EVA) or Mondini’s dysplasia that may be associated with Pendred’s syndrome
-In cases of suspected BOR, a renal ultrasound should be performed

Question 15

what is screening ?

Answer 15

Tests used to IDENTIFY people with a high risk of having a specific genetic disorder

Question 16

what is diagnostic ?

Answer 16

-Tests performed that confirm or exclude a known/suspected genetic disorder in an individual showing symptoms
-Also can be performed prenatally in a fetus at-risk for a certain genetic conditions

Question 17

what is genetic evaluation?

Answer 17

Genetic tests are typically performed by a trained genetic technicians

Question 18

what is an example of genetic testing?

Answer 18

genomic sequencing

Question 19

genetic test involve?

Answer 19

-A detailed clinical and family history
-Comprehensive examination of patient and if necessary, parents and siblings by a physician

Question 20

what is the rationale of GJB2 testing to be the first step in genetic testing ?

Answer 20

BECAUSE IT’S SO COMMON
-It identifies the genetic nature of “sporadic cases”
-It allows for accurate counseling
-It highlights the need for early language and speech intervention
-It avoids further diagnostic tests and maintains cost efficiency
-It suggests that the hearing loss is not at increased risk for medical co-morbidities

Question 21

what can we do to diagnose a child with hearing loss?

Answer 21

-Newborn hearing screening
-Confirmation of hearing loss (diagnostic ABR)
-Obtaining a detailed family history
-ENT, audiology, and genetic evaluation
-Molecular testing for GJB2/GJB6 mutations – first step for genetic testing
- If negative, follow up with:
-Cranial imaging studies (if EVA +ve, then test for Pendred genes)
-Cardiac evaluation/EKG (rule out long QT interval)
Ophthalmologic evaluation
-Guided molecular testing for hearing loss genes - OtoSCOPE

Question 22

what is an otoSCOPE?

Answer 22

(Otologic Sequence Capture of Pathogenic Exons) genetic panel for hearing loss
it includes:
Comprehensive tests for 152 genes known to cause
-Non-syndromic hearing loss
-Usher and Pendred syndrome
-Other hearing loss-related phenotypes
-Tests for both GJB2 and GJB6 genes
-Tests for both AR and AD conditions
-Fast and accurate – 99% diagnostic specificity
-Uses the next generation sequencing method

Question 23

who should be tested?

Answer 23

parents and grandparents

Question 24

what are some “do”s fro diagnosing a HL

Answer 24

-Detailed family history
-Consider genetic etiology
-Rule out syndromic HL
-DNA testing for GJB2/GJB6 genes
-Temporal bone imaging

Question 25

what are don’t to diagnosing HL?

Answer 25

-Call it sporadic or environmental
-Quote a negligible recurrence risk
-Offer a molecular panel for HL at the outset

Question 26

what are some clinical benefits of identifying genetic conditions?

Answer 26

-Provide professionals with an ability to make an accurate diagnosis and prognosis
-Provide scientific explanations of why the problem occurred, and therefore, preventing/removing the blame game
-Recognition of the risk of associated structural anomalies (e.g., congenital heart defects)
-Recognition of the risk of associated developmental handicaps (e.g., learning & intellectual disability)
-Provide accurate recurrence risk for off springs

Question 27

what are some psychosocial and ethical issues in genetic testing ?

Answer 27

-Genetic testing is very specific but it is not sensitive
-Provides information affecting reproductive choices
-Provides information about biologic relatives
-insurance discrimination
-Genetic testing and the Deaf community
-they don’t like it cause they think you’re trying to fix the problem

Question 28

what is misassigned paternity ?

Answer 28

dad is not dad

Question 29

who can provide genetic counseling ?

Answer 29

pediatrician or internist working with a genetic counselor

Question 30

what should formally be done with genetic counseling because of how problematic it is

Answer 30

Because of the potential ethical, emotional, and psychosocial issues associated with genetic testing, formal pre-test counseling is as important as post-test counseling

Question 31

what is something good about genetic counseling?

Answer 31

Counseling also ensures that those who receive genetic testing have a clear understanding of its meaning, including risk of recurrence and how that risk can change

Question 32

do audiologist do genetic counseling?

Answer 32

no, we refer to genetic counseling

Question 33

why is an audiologist so important in being a part of genetic counseling?

Answer 33

Although audiologists may not provide direct genetic counseling they are often the first line of professionals who encounter individuals with genetic hearing loss