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Genetics and Primary Care

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The Human Genome Project has brought inherited health factors to the forefront ... Use Hb electrophoresis (NOT sickle dex) Standard to review MCV ... – PowerPoint PPT presentation

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Title: Genetics and Primary Care


1
Genetics and Primary Care
  • Cystic Fibrosis and Ethnicity-Based
  • Carrier Screening

2
Genetics in Health Care the 21st Century
  • The Human Genome Project has brought inherited
    health factors to the forefront
  • Genetic risk assessment, screening and testing is
    becoming part of primary medical care
  • Clinical genetics and primary care need to work
    together to offer appropriate services

3
We are Working Together
  • Risk assessment for common genetic conditions
  • likely to be performed in the primary
    care/prenatal setting
  • Screening and testing for genetic conditions
  • increasingly performed in primary care/prenatal
    care
  • Patients with rare or more complex genetic
    conditions, risks, or family histories
  • likely continue to be served by genetics
    specialists

4
Outline
  • Principles of genetic carrier screening
  • Cystic fibrosis carrier screening
  • Screening guidelines for other ethnic groups
  • Ethical issues in carrier screening
  • Resource Information

5
Genetics Review
  • Most carrier tests are for autosomal recessive
    conditions (some for X-linked)
  • In general, carriers of autosomal recessive
    conditions do not have symptoms and remain
    unaffected
  • Both partners must be carriers to have a child
    with an autosomal recessive condition
  • Review of autosomal recessive inheritance

6
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7
Carrier Screening
  • Population-based screening
  • Particular genetic carrier tests offered to
    everyone in the general population
  • Targeted population-based screening
  • Carrier screening limited to particular groups of
    people determined to be at higher risk for
    specific genetic disorders
  • e.g. Ethnicity-based carrier screening

8
Carrier Testing
  • To determine an individuals carrier status for a
    specific genetic disease
  • Not usually offered on a population basis

9
Carrier Testing
  • Available to clients with a family history of an
    autosomal recessive or X-linked genetic condition
    for which carrier testing available
  • e.g. Fragile X syndrome, Duchenne muscular
    dystrophy, Hemophilia A or B
  • e.g. PKU, Alpha-1-antitrypsin deficiency,
    Galactosemia

10
Ethnicity-Based Genetic Carrier Screening
  • Purpose To detect couples at risk for prenatally
    diagnosable genetic diseases
  • Types of tests offered based on clients ethnic
    background
  • Offered to all individuals of that ethnic
    background (targeted population screening)

11
Carrier Frequencies based on Ethnic Origin
Condition
Carrier Frequency
Population
12
Principles of Carrier Screening
  • Should be offered to patients
  • Seeking preconception counseling, OR
  • Seeking infertility care, OR
  • During the first or early second trimester of
    pregnancy

13
Timing
  • Offering screening prior to pregnancy allows
    client more reproductive choices
  • Screening during pregnancy
  • Depends on gestational age
  • If early in pregnancy, can do sequential
    screening
  • Concurrent testing is an option if later
    gestational age

14
Informed consent
  • Counseling before screening should include
  • Purpose, voluntary nature of screening
  • Range of symptoms and severity of each disease
  • Risk of carrier status and affected offspring
  • Meaning of positive and negative results
  • Factors to consider in decision-making
  • Further testing would be necessary for prenatal
    diagnosis

15
Informed consent
  • Utilize patient resources materials
  • Patient brochures about CF and other
    ethnicity-based genetic screening available from
    multiple sources
  • Carrier screening videos can be shown in office
    settings
  • Document informed consent discussion and patient
    decision

16
Carrier Screening Resources
  • March of Dimes Genetic Screening Facts
  • Patient brochures
  • CF screening, Ashkenazi Jewish ethnicity based
    carrier screening, MOD fact sheets
  • www.genetests.com - list of labs offering carrier
    testing for specific genetic disorders

17
Important Points
  • Carrier screening is optional
  • Patient education/informed decision-making is
    essential
  • Most tests detect a majority but not all carriers
  • Screening may or may not be covered by insurance
    (not covered by OHP and some other major
    insurers)
  • Genetic counseling is available and advised for
    carriers and carrier/carrier couples

18
Cystic Fibrosis
  • Chronic lung disease with GI malabsorption
  • Incidence of 1/3300 in Caucasian and AJ
    populations
  • Age of onset early childhood. Variable symptoms.
    Life expectancy now 20-35 years
  • Treatment daily respiratory therapy, digestive
    enzymes, medication to promote lung function

19
CF Carrier Screening
  • 1/25-1/29 carrier rate in general Caucasian
    population
  • Same in Ashkenazi Jewish population
  • Carrier screening by DNA mutation analysis. ACOG
    suggests panel of 25 most common mutations
  • Some labs do additional mutations but at higher
    cost
  • Detection rate in AJ population is 97
  • Detection rate in Caucasian population is 80-90
  • Preconception and Prenatal Carrier Screening for
    Cystic Fibrosis The American College of
    Obstetricians and Gynecologists, Oct. 2001.

20
CF Carrier Screening
  • ACOG guidelines, Oct. 2001
  • Offer CF screening to
  • Individuals with a family history of CF
  • Reproductive partners of carriers/persons with CF
  • Couples in whom one or both partners are
    Caucasian and are planning a pregnancy or seeking
    prenatal care
  • Make CF screening available to couples in other
    racial or ethnic groups at lower risk

21
CF Carrier Results
  • Many tests detect a majority but not all carriers
  • Detection rates differ by ethnicity
  • Negative results do not eliminate risk
  • Different mutations may confer different risks
  • Example CFTR R117H mutation and 5T allele
  • Genetic consultation is available to carriers and
    strongly advised for carrier/carrier couples

22
Carrier Rates Cystic Fibrosis
23
Issues in CF Screening
  • Variable severity and symptoms mild vs. classic
    mutations
  • Know the details about the mutation before
    discussing results with the patient
  • Potential to detect an affected person through
    screening (i.e. person having two mutations and
    mild or no symptoms)

24
Issues in CF Screening
  • Congenital absence of the vas deferens (CAVD) as
    a mild manifestation of CF
  • Should this be discussed with clients? Tested
    for?
  • Prenatal testing for women who are carriers when
    father of baby not available for carrier testing
    risks/benefits
  • Rare chance of uncovering non-paternity

25
CF screening case study
  • Marcia is a 25 year old Caucasian woman who comes
    to her first prenatal visit at 9 weeks gestation.
    Her husband, Mark, age 28, also Caucasian,
    attends the visit with her. There is no family
    history of significance.
  • Her prenatal care provider, Ann Smith, NP,
    discusses the option of CF carrier screening with
    the couple.

26
Case Study Informed Consent
  • NP Smith discusses
  • The symptoms and natural history of CF
  • The risk of being a CF carrier is 1/29 for
    individuals of Caucasian ancestry
  • The risk of both members of this couple being CF
    carriers is 1/840
  • The risk of having an affected child is 1/3300
    (before testing)

27
Case Study Informed Consent
  • The risk of the fetus having CF if both are
    carriers is 25. Options in this case
  • amniocentesis to determine the status of the
    fetus
  • waiting until birth
  • The risk of the fetus having CF if one is a
    carrier and the other has a negative screen is
    1/560
  • The risk of the fetus having CF if both have
    negative screen results is 1/78,400
  • Preconception and Prenatal Carrier Screening for
    Cystic Fibrosis ACOG/ACMG, Oct 2001

28
Case Study Informed Consent
  • Carrier screening is optional
  • Insurance may or may not cover CF screening
  • Their gestational age is early enough that they
    have the option of sequential vs. concurrent
    screening
  • Ms. Smith gives the couple the PacNoRGG brochure
    entitled Should I Have a Cystic Fibrosis Carrier
    Test?

29
CF Case Study Results
  • Marcia and Mark decide to have CF screening
  • Results
  • Marcia has a deltaF508 mutation and is a CF
    carrier
  • Mark is negative for the 25 mutation panel
  • NP Smith informs couple of results
  • Marcia is a carrier of a common CF mutation. It
    will not affect her health
  • Mark has a negative screen residual carrier risk
    is 1/140

30
Case Study Results Counseling
  • The residual risk of CF in this fetus and in
    future pregnancies of theirs is 1/560
  • The chance for each of Marcias siblings to be
    carriers of the same mutation is 50
  • The couple is given the PacNoRGG brochure
    entitled So I Have a Cystic Fibrosis Gene, But
    My Partners Test was Negative
  • NP Smith encourages Marcia to inform her siblings
    and parents of her carrier status

31
Ashkenazi Jewish patients
  • Standard of care to offer to persons of AJ
    background and/or their partners
  • Tay-Sachs disease
  • Cystic Fibrosis
  • Canavan disease
  • Familial Dysautonomia
  • All autosomal recessive genetic conditions

32
Tay-Sachs Carrier Testing
  • Progressive, fatal neurodegenerative condition
    with no treatment
  • 1 in 30 carrier rate (AJ)
  • Carrier screening
  • Enzyme based (Hex A) 98 detection rate
  • pregnant women leukocyte or platelet test
  • DNA based 94 carrier detection rate
  • www.ntsad.org

33
Canavan Carrier Testing
  • Progressive neurodegenerative disease Onset
    infancy/childhood Usually fatal by 10 yr No
    treatment or cure
  • 1 in 40 carrier rate (AJ)
  • Carrier screening by DNA mutation analysis
  • 98 carrier detection rate in persons of AJ
    ancestry
  • www.ntsad.org

34
Familial Dysautonomia
  • Sensory and autonomic neuropathy (AR)
  • Lack of tears decreased reaction to pain and
    taste abnormal temperature and blood pressure
    control GI dysmotility dysphagia excessive
    sweating motor coordination problems
  • Normal intelligence
  • 1 in 27 carrier rate in AJ population
  • Now part of the standard panel offered to people
    of Ashkenazi ancestry
  • Obstet Gynecol 2004 Aug 104(2)425-8. ACOG
    Committee Opinion Number 298

35
Other Carrier Tests Available to Persons of AJ
Descent
  • Bloom syndrome
  • Fanconi anemia group C
  • Gaucher disease, type 1
  • Niemann-Pick, type A
  • Mucolipidosis IV
  • Others? (Von Gierke disease, hereditary deafness,
    torsion dystonia)

36
Hispanic/Latino patients
  • No standard protocol for carrier testing
  • Cystic Fibrosis carrier rate 1/46
  • Beta-thalassemia carrier rate 1/30 to 1/50
  • Sickle cell or other hemoglobin trait
  • Carrier rate 1/30 (Caribbean) to 1/200

37
Asian patients
  • Standard to review MCV. If thalassemia w/quantitative Hb electrophoresis
  • Alpha-thalassemia carrier rates up to 1/20
  • Beta-thalassemia carrier rates 1/30 (SE Asian) to
    1/50
  • Cystic fibrosis carrier rate 1/90 or less
  • Detection rate is very low ( 30)
  • Not standard to do CF screening
  • Make available upon patient request

38
African-American patients
  • Standard to offer Sickle Cell screening
  • Sickle cell carrier rate about 1/10 to 1/12
  • Use Hb electrophoresis (NOT sickle dex)
  • Standard to review MCV
  • Beta-thalassemia carrier rate about 1/75
  • If MCV w/quantitative Hb electrophoresis
  • CF carrier rate about 1/65
  • no standards re offering CF carrier screening

39
Who to Refer to Genetics
  • Individuals with a family history of cystic
    fibrosis or other autosomal recessive disease
  • Couples where both members are known carriers for
    an autosomal recessive disease
  • Couples where one member is a carrier and has
    additional questions
  • Pregnant carriers who do not have results on the
    father of baby

40
Oregon Genetics Providers
  • Portland
  • Oregon Health Science University
  • Legacy Health Care
  • Northwest Perinatal Services
  • Kaiser-Permanente
  • Eugene
  • Center for Genetics Maternal Fetal Medicine
  • Bend
  • Genetic Counseling of Central Oregon (cancer only)

41
How, When, Where
  • How? Give a center a call
  • When? ASAP
  • Where? Oregon Genetics Clinics Contact List

42
Resource Information
  • Provider and patient education materials
  • Genetic Web Site Reference List
  • Patient brochures
  • www.genetests.com - list of labs offering carrier
    testing for specific genetic disorders

43
ADDITIONAL INFORMATION
44
Family History Questionnaire
  • Screens for reproductive genetic risks
  • Appropriate for patients considering pregnancy or
    already pregnant
  • Contains referral guidelines for genetic services

45
Assessment Areas
  • Maternal age
  • Family medical history (both sides)
  • Current pregnancy/pre-pregnancy history
  • Ethnic background (both sides)

46
Who To Refer Prenatal Genetic Services
  • Advanced maternal age
  • Abnormal serum marker screening results
  • Fetal abnormalities on prenatal ultrasound
  • Personal or family history of a known or
    suspected genetic disorder, birth defect, or
    chromosome abnormality
  • Family history of mental retardation of unknown
    etiology
  • Patient with a medical condition known or
    suspected to affect fetal development

47
Who to refer (cont)
  • Exposure to a known or suspected teratogen
  • Either parent or family member with a chromosome
    rearrangement
  • Parent a known carrier or has a family history of
    a disorder for which prenatal testing is
    available
  • Unexplained infertility or multiple pregnancy
    losses or previous stillbirths
  • Absence of the vas deferens
  • Premature ovarian failure
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