SCREENing Kathy Morris mssw lcgc Senior genetic counselor objectives Know current ACOG guidelines about genetic disease carrier screening Name 3 ethnicspecific genetic diseases Know how to order or arrange carrier screening ID: 913580
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Slide1
Genetic disease carrier SCREENing
Kathy Morris,
mssw
,
lcgc
Senior genetic counselor
Slide2objectives
Know current ACOG guidelines about genetic disease carrier screening
Name 3 ethnic-specific genetic diseases
Know how to order or arrange carrier screening
Understand the role of a genetic counselor in facilitating carrier screening
Slide3Case 1-alicia
Alicia is a 24 year old G2P1 who is here for her first OB visit. She has African American and Hispanic ancestry. She is unaware of any family history of sickle cell disease. The father of the pregnancy is Hispanic from Cuba.
Do you offer or order any carrier testing?
Why or why not?
If yes, for what do you test her and what test(s) do you order?
Slide4Case 2-sarah
Sarah is a 32 year old G1 who presents for OB care. Her family history questionnaire reveals that she has Ashkenazi Jewish ancestry. She has no known family history of
Tay
Sachs or other “Jewish” genetic diseases. Her partner is of mixed northern European Caucasian ancestry.
Do you order or offer any carrier screening?
Why or why not?
If yes, for what do you test her?
Slide5Case 3-JENNIFER
Andrea is a 32 year old who comes for a well-woman exam. She and her partner are thinking about having a baby. She is of non-Jewish northern European Caucasian ancestry and the partner is of Native American (Zuni) heritage. She requests cystic fibrosis carrier testing.
Do you think she needs CF carrier screening?
If yes, do you think she should be tested now or wait until she’s pregnant?
Why?
If yes, do you just test her, or test her and her partner at the same time?
Slide6Case 4-sandra
Sandra is a G3P2 woman who comes for her first prenatal visit. She is of Chinese ancestry, as is her husband. She has a history of anemia, previously treated with iron, but not re-evaluated after therapy.
Do you order or offer her any carrier screening for genetic diseases?
Why or why not?
If yes, for what do you screen her?
Slide7Case 5- ASMAE
Asmae
and Ahmad are expecting their third baby, though it’s the first time you’ve seen them for care. They are Lebanese and are first cousins. The other two children are healthy. There is no known family history of genetic disease.
Do
you
order or offer
any carrier
screening
?
Why or why not?
If yes, what do you test
for
?
Slide8Carrier screening
Decisions about carrier screening historically based on ethnicity
“It
is becoming increasingly difficult to assign a single ethnicity to
individuals”*
Professional organizations offer limited guidance
*
2011 Update: ACOG Committee on Genetics
Opinion CF Carrier testing
Slide9ACOG RECOMMENDATIONSCystic fibrosis
2001: ACOG and ACMG guidelines
for prenatal and preconception carrier screening for
CF
Offer to
Non-Hispanic Caucasians and people of Ashkenazi Jewish
ancestry
Panel
of 25 known
disease-causing
mutations
Should be made available to all women
of childbearing age, regardless of ethnicity.
2011 Update: ACOG Committee on Genetics Opinion:
Offer CF
screening
to all women
of reproductive age
.
“…increasingly
difficult to assign a single ethnicity to individuals
.”
CF screening
is most efficacious in the non-Hispanic white and Ashkenazi Jewish populations.
Slide10ACOG RECOMMENDATIONS*Ashkenazi
jewish
RECOMMEND SCREENING FOR
Tay
Sachs disease 1/30
Cystic fibrosis 1/30
Familial
dysautonomia
1/30
Canavan
disease 1/40
Before
conception or during early
pregnancy
May be
necessary to screen both partners
simultaneously
* ACOG Committee Opinion, October, 2009
Slide11ACMG recommendationsAshkenazi
jewish
Gaucher
disease, Type I 1/18
Tay
Sachs disease 1/30
Familial
dysautonomia
1/30
Canavan
disease
1/40
Niemann
-Pick syndrome, Type A
1/90
Bloom syndrome 1/100
Mucolipidosis
IV
1/130
Slide12Population screening guidelines*
The disorder impairs health in the homozygous affected offspring.
There is a high frequency of carriers in the screened population.
Technically and clinically valid screening methods are available and cost effective to all.
IVF, prenatal diagnosis, and termination are reproductive options.
Consent (informed and voluntary participation) is obtained.
Potential benefits and risks of carrier testing are communicated before and after the test.
Privacy is protected.
Stigmatization of the carrier by the community is minimized.
Experienced professional resources are available.
*NHGRI conference on population carrier screening, 2008
Slide13Carrier FREQUENCY
Certain
diseases/gene mutations
are
more prevalent in certain populations, but they do occur in
others*
TAY SACHS DISEASE CARRIER
1/30
of Ashkenazi ancestry
1/50 Irish ancestry (?)
1/53 French Canadians
1/300 non Ashkenazi
“Ancestry Based Carrier Screening,” NSGC, 2005
Slide14CARRIER FREQUENCY
Certain diseases/gene mutations are more prevalent in certain populations, but they do occur in others*
CYSTIC FIBROSIS CARRIER
1/13
Zuni Native American
1/25 northern European Caucasians
1/30 Ashkenazi Jewish
1/50 Hispanic
1/65 African American
1/90 Asian American
* “Ancestry Based Carrier Screening,” NSGC, 2005
Slide15CARRIER FREQUENCY
Certain
diseases/gene mutations are more prevalent in certain populations, but they do occur in others
*
HEMOGLOBINOPATHIES
1/10 from Jamaica or Haiti has sickle cell (S) trait
1/10 African Americans has
ᵝ
thalassemia
trait
,
1/12 has S
trait, 1/33
Hb
C trait
1/42 Cubans has S trait
1/67 from Mexico have S trait
1/120
Caucasians has S trait
1/20 people of Mediterranean ancestry has
ᵝ
thalassemia trait
1/30 Chinese have
ᵝ
thalassemia
trait, 1/20 have
α
thalassemia trait
*
“Ancestry Based Carrier Screening,” NSGC, 2005
Slide16Carrier screening
Some diseases occur with equal frequency across ethnic groups
Spinal
Muscular Atrophy
1/40 – 1/60
across
ethnicities
Glycogen Storage
Diseases 1/75
Wilson’s disease 1/86
Fragile
X syndrome
1/260
women carries a
FraX
pre-mutation
Slide17Symptomatic carriers
SICKLE CELL TRAIT
Propensity to urinary tract infection in women*
Gross hematuria**
Splenic infarction with altitude hypoxia or exercise**
ᵝ
THALASSEMIA TRAIT
mild microcytic anemia, does not respond to iron
FRAGILE X
Premature ovarian failure 15-20%
Fragile X tremor-ataxia syndrome 5-10%
IJOG, 2006, 92, 128-129
** Oman Medical Journal, Jan. 2010; 25 (1), 3-8
Slide18When to screen?
Ideally done prior to conception
Couples at risk can make decisions about whether or not to become pregnant, or to use alternative reproductive strategy
Prenatal diagnosis
Sperm donor
Ovum donor
Preimplantation genetic diagnosis (PGD)
Adoption
Remain childless
Slide19Whom to offer screening?
ANYONE!
Most are autosomal recessive diseases
Carriers are usually asymptomatic
We all carry several gene mutations which could lead to serious illness in our children
Most children with autosomal recessive diseases are born to couples with no family history
Useful for consanguineous couples with no family history
Do not
just consider screening in someone with a family history
*Thompson and Thompson,
Genetics in Medicine
, 2007, pp. 122-124
Slide20Carrier testing-WHAT KIND OF TESTING?
M
olecular genetic testing
, in which gene mutations are sought
Excellent for ethnic-specific mutations
Can be expensive
Biochemical or other
testing-preferable in some cases, often less expensive
Hexosaminidase
A assay:
Tay
Sachs screening for non-Ashkenazi
Hemoglobin electrophoresis and CBC for
hemoglobinopathies
Slide21SCREENING ALGORITHM
FOR HEMOGLOBINOPATHIES*
*Ancestry Based Carrier Screening, NSGC, 2005
Slide22One disease or many?
Depends on cost and family’s desires
Molecular genetic testing (sequencing or targeted mutation testing) for a single disease can be expensive
More economical to screen for many diseases at once
Slide23Carrier test panels- aSHKENAZI JEWISH
Emory “
JScreen
”
20 diseases $ 600 or $1000
Progenity
“AJ
Nxt
Complete” 38 diseases $400-$600
Integrated Genetics “
Inheritest
select” ~90 diseases $850
Tricore
CF only 1 disease $600
LABS OFTEN OFFER DISCOUNTS FOR SELF-PAY OR FINANCIAL HARDSHIP
Slide24Carrier test panels
PAN-ETHNIC/UNIVERSAL
Counsyl
101 diseases, can
customize $
99-$299 with insurance
Emory >140
diseases 2 tiered $600 or $1000
Integrated Genetics “
Inheritest
,” ~90 diseases $
950
Natera
“Horizon” 38 diseases $100-$200
pt
cost
GenPath
, “
InheriGen
,” 160 disorders $395-$495
Pathway Genomics, > 70 AR diseases Would not disclose price
Progenity
, 3
diseases $200-$300
LABS OFTEN OFFER DISCOUNTS FOR SELF-PAY OR FINANCIAL HARDSHIP
Slide25Role of Genetic counselor
Familiar with ethnic-related genetic diseases
Skilled at patient education, exploring patient desires and priorities
Familiar with how to order tests for rare genetic
diseases
Familiar with financial arrangements from various labs
Able to devote time to detailed discussion
Just put a referral in ad hoc
Slide26REFERRAL FOR GENETIC COUNSELING
Ad hoc
Women’s Ultrasound OB
Check Genetic Counseling
Menu comes up
Slide27Case 1-alicia
Alicia is a 24 year old G2P1 who is here for her first OB visit. She has African American and Hispanic ancestry. She is unaware of any family history of sickle cell disease. The father of the pregnancy is Hispanic from Cuba.
Do you offer or order any carrier screening?
Why or why not?
If yes, for what do you test her and what test(s) do you order?
Slide28Case 2-sarah
Sarah is a 32 year old G1 who presents for OB care. Her family history questionnaire reveals that she has Ashkenazi Jewish ancestry. She has no known family history of
Tay
Sachs or other “Jewish” genetic diseases. Her partner is of mixed northern European Caucasian ancestry.
Do you order or offer any carrier testing?
Why or why not?
If yes, for what do you test her?
Slide29Case 3-JENNIFER
Andrea is a 32 year old who comes for a well-woman exam. She and her partner are thinking about having a baby. She is of non-Jewish northern European Caucasian ancestry and the partner is of Native American (Zuni) heritage. She requests cystic fibrosis carrier testing.
Do you think she needs CF carrier screening?
If yes, do you think she should be tested now or wait until she’s pregnant?
Why?
If yes, do you just test her, or her and her partner at the same time?
Slide30Case 4-sandra
Sandra is a G3P2 woman who comes for her first prenatal visit. She is of Chinese ancestry, as is her husband. She has a history of anemia, previously treated with iron, but not re-evaluated after therapy.
Do you order or offer her any carrier screening for genetic diseases?
Why or why not?
If yes, for what do you screen her?
Slide31Case 5- ASMAE
Asmae
and Ahmad are expecting their third baby, though it’s the first time you’ve seen them for care. They are Lebanese and are first cousins. The other two children are healthy. There is no known family history of genetic disease.
Do
you
order or offer
any carrier
screening
?
Why or why not?
If yes, what do you test
for
?
Slide32QUESTIONS?
COMMENTS?