genetic testing and psychosocial/ ethical issues and genetic couseling Flashcards
what is assortative mating ?
Mating of people with the same phenotype resulting in more of the phenotype than expected by chance
ex. the deaf community?
what is linguistic homogamy ?
Mating between individuals that have the same language such as “native” signers
what is the founder effect ?
-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
what is population bottleneck?
-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
what is balanced polymorphism?
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
how to identify a HL with perinatal history
-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)
what else could help identify an affected individual?
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
how is family history help identify affected individuals
-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
how can physical examination help identify affected individuals ?
-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
what are some audiological test to help us identify audiologic findings?
-OAE/ABR for young children
-Audiogram/behavioral assessment for older children
-Presence or absence of hearing loss in other family members should be documented
how can lab test help us identify an affected individual
-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)
how can endocrine function help identify with affected individuals ?
-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
how can electrocardiograms help identify affected individuals ?
Calculation of the QT interval if family history of syncope or sudden infant death, which may be an indication of JLNS
how can radiology help identify affected individuals?
-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
what is screening ?
Tests used to IDENTIFY people with a high risk of having a specific genetic disorder
what is diagnostic ?
-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
what is genetic evaluation?
Genetic tests are typically performed by a trained genetic technicians
what is an example of genetic testing?
genomic sequencing
genetic test involve?
-A detailed clinical and family history
-Comprehensive examination of patient and if necessary, parents and siblings by a physician
what is the rationale of GJB2 testing to be the first step in genetic testing ?
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
what can we do to diagnose a child with hearing loss?
-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
what is an otoSCOPE?
(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
who should be tested?
parents and grandparents
what are some “do”s fro diagnosing a HL
-Detailed family history
-Consider genetic etiology
-Rule out syndromic HL
-DNA testing for GJB2/GJB6 genes
-Temporal bone imaging
