11/5- Genetic Counseling and Risk Flashcards
In what ways are genetic conditions different from other medical conditions?
- Predicting future health
- Invasion of privacy
- Life and death issues faced in prenatal decisions
- Potential discrimination
- Effect/risk to other family members
- Lack of treatment/interventions*
Genetic conditions are not always inherited (some occur de novo)
What is genetic counseling/what are the goals?
Communication process which deals with the human problems associated with the occurrence of risk of a genetic disorder in a family. Goals are to help the individual or family to:
- Comprehend medical facts
- Appreciate the way heredity contributes to the disorder and the risk of recurrence in specified relatives
- Understand options for dealing with risk of recurrence
- Choose a course of action which seems to them appropriate in view of their risk, their family goals, and their ethical and religious standards
- To make the best possible adjustment to the disorder in an affected family member and/or to the risk of recurrence of that disorder
What are indications for genetic counseling?
- Questions of diagnosis, cause, and prognosis of heritable or developmental disorders
- Questions of disease risk for family members
- Questions of the risk for a genetic disease in an expected or future child
- Discussions of options of prenatal testing for certain genetic disorders
- Discussions about and performance of predictive molecular genetic testing (e.g., for cancer disposition syndromes or for late manifesting heritable diseases such as Huntington disease)
- Questions of management and anticipatory guidance for heritable disorders or disease susceptibility
- Clarification and advice about:
- Infertility or recurrent miscarriages
- Advanced maternal or paternal age
- Assisted reproductive therapy
- Marriage between relatives (consanguinity)
- Exposure to teratogens before or during pregnancy
What are some reasons for referral to genetic counseling?
- Prenatal
- ART, Male or Female Infertility
- Pediatric: Abnormal newborn screening results, child with birth defect, neurologic disorders, ID/DD, FTT, short statures, autism spectrum disorders, hearing loss, vision loss
- Cancer: Individuals with a personal or family history of cancer (especially those with multiple affected family members and cancer at unusually young ages)
- Metabolic: diagnosis, treatment and follow-up for IEMs, couples who have had children died of SIDS or SUDC
- Neurogenetics: Patients with suspected or known neurogenetic conditions or with a family history of hereditary neurogenetics condition (i.e., DMD, ALS, HD,)
- Hematology: Individuals who have a diagnosis or family history of a hematologic condition (i.e., sickle cell, Fanconi anemia)
- CV genetics: Suspected or known hereditary cardiovascular disease or with a family history of hereditary cardiovascular disease (i.e., Long QT, Marfan, HCM, sudden cardiac death under 50yo)
What is the structure of a genetic counseling visit?
Information, education; “Talking”:
- Information gathering
- Information giving
- Communication of Risk
Counseling, support; “Listening”:
- Psychosocial assessment and counseling
- Help with decision making
- Ongoing client support
What are some key points regarding communication of risk in genetics counseling?
- Risk communication is an integral part of genetic counseling
- Help an individual make a choice about whether or not to undergo testing
- Help individuals and families adjust to the knowledge that an event has occurred.
- People’s perception of the magnitude of risk are influenced by factors other than numerical data
- Terms such as risk, chance, possibility, or probability also imply value judgments (e.g., risk = bad, chance = good), which may be perceived differently by different individuals
- 1/800 sounds higher than 1/400 since denominator is higher
- Use of nonnumeric phrases (often, rarely, never) introduces potential risk for bias
What are the best practices to use when communicating risk?
- Provide risk in several ways
- Provide likelihood of a negative outcome balanced by the likelihood of a positive outcome
- Use visuals to emphasize key points
- Use risk comparisons to help put risks in perspectives
- Abstractions: use examples, stories, analogies
- Fractions, percent
- If risk is unclear, give a range
- Assess patient’s perception of risk – more meaningful than the actual risk
- Define technical terms, use words the patient is familiar with
- Be cautious of nonverbal messages
What are some counseling skills/behaviors?
- Sit if possible
- Effective listening
- Promote shared language
- Silence
- Rephrasing: stating in your own words what the pt has said
- Reflecting: repeating the last phrase of a client’s statement in the form of a question
- Redirecting: used to manage the rate of information exchange
What are the different types of responses you may get?
- Factual responses
- Aggressive/hostile response (“counterattack”; by patient)
- Reassuring response (by doctor; but don’t do before concerns are heard)
- Empathetic response
What are some common pitfalls made be doctors in counseling?
- Wanting to be liked
- Asking too many closed-ended questions
- Reluctance to control the agenda
- Avoiding emotionally charged issues
- Bringing your own agenda/biases into the session
What are some themes in genetic counseling?
- Non-directive
- Autonomy
- Informed Consent
- Confidentiality
- Beneficence (non-maleficence)
What are different methods of risk assessment
Straight forward risk assessment, use:
- Inheritance/pedigree analysis to estimate risk
- Hardy-Weinberg to estimate risk
- Genotype to estimate risk
Not as straight forward:
- Recurrence risks can be more difficult to assess if inheritance patterns are affected variable expression, reduced penetrance, under 100% sensitivity of molecular testing, new mutations
- Use Bayesian analysis
What are some inheritance patterns?
- Single gene inheritance
- Non-traditional inheritance patterns
Single gene inheritance
- Autosomal dominant
- Expressivity and penetrance
- Autosomal recessive
- X-linked
Non-traditional inheritance patterns
- Multifactorial
- Mitochondrial
- Trinucleotide repeat
- Uniparental disomy
- X-inactivation
What is the Hardy Weinberg Law?
- Assumptions
- Genotypes are distributed in proportion to the frequencies of the individual alleles in a population and remain constant from generation to generation if the population is at equilibrium
- Using genotypes, can calculate allele frequencies
- Assumptions:
- Random mating
- No selection
- No new mutations
- Population is infinitely large
- No migration
- If these assumptions are nearly correct, the locus is said to be in Hardy Weinberg equilibrium
How to calculate allele frequency
Ex) MN blood group system genotypes (M/M, M/N, N/N)
- What is frequency of M allele? N? (pic 496 )
- Multiply number of individuals with M/M genotype by 2 since each individual has 2 M alleles.
- Similarly, multiply total number of individuals in population by 2 since each individual has 2 alleles/chromosomes
What is the Hardy Weinberg equation?
- What do the variables stand for?
- For A/a autosomal dominant alleles, how do you calculate frequency of AA? Aa? aa?
Calculate the frequency of M/M, M/N, and N/N genotypes for the past example
How closely the numbers calculate match the genotype counting method determines whether the population is at equilibrium
Look at this analysis of the HW equation for an autosomal dominant trait
Look at this analysis of the HW equation for an autosomal recessive trait
Cystic fibrosis affects approximately 1/2,500 non-Jewish, Caucasians in the US. What is the frequency of the CF gene and what is the frequency of heterozygotes (CF carriers)?
- For rare recessive traits (incidence under 1/10,000), p, the frequency of the normal allele is very close to one and the carrier frequency equals 2q.
- Therefore, for AR traits, the frequency of the mutant allele is the square root of the incidence (q2) and the carrier frequency is 2q(1-q) or 2q for rare traits.
What is the equation for X-linked traits:
- Males
- Females
Example risk calculation using Bayesian Analysis for the following:
- Prior probability
- Conditional probability
- Joint probability
- Posterior probability
Example of Bayesian analysis:
- Mary wants to know if she is a carrier of DMD
- Mary is the daughter of an obligate carrier (both her maternal uncle and brother have DMD)
- Mary has 4 sons, all are healthy
- Prior probability for situation A (carrier) and situation B (no carrier). The probability for each of these situations is 1/2. The two events are mutually exclusive; therefore, their sum is 1/2 + 1/2 = 1.
- The conditional probability that four sons of a carrier are healthy is (1/2)4 = 1/16 (with a probability of 15/16 that at least one of the sons would have been affected).
- Since the various pregnancies represent mutually independent events, the multiplication rule is applied. In the case that person B is not a carrier for muscular dystrophy, she would only have healthy sons. The conditional probability in this case is 1.
- All this information is taken into account in the calculation according to the Bayes theorem as shown in Table 14.2. This results in an posterior probability of approximately 1/17 for situation A that she is a carrier, and in an posterior probability of 16/17 that she is not a carrier. This example demonstrates the considerable change in risk figures once all relevant information is taken into account.
Example: Bayes + Hardy Weinberg The Potters have 2 healthy children. Mrs. Potter has found out that her niece has CF.
- What is the probability that they have an affected child if the healthy children are taken into consideration?
Use BAYES!
- The chance that BOTH parents are carriers is about 1/88
- Therefore, the chance to have a future child with CF is about 1/350 (0.3%)
