THE VALUE OF FAMILY
HISTORY IN THE PRENATAL
CARE SETTING
INSERT PRESENTATION DATE
Agenda
Value of family history (FmHx)
FmHx collection tools
“Red flags”
Risk assessment and management guidelines
Case studies
Acknowledgements
Curriculum reviewers
Funded through grant # U33MC12786 from the Health Resources and Services Administration
Value of Family History
Grandparents’
generation
Paternal
Grandfather
Paternal
Grandmother
Maternal
Grandfather
Maternal
Grandmother
Parents’
generation
Paternal
Uncle
Dad
Mom
Maternal
Uncle
My generation
Paternal
Cousin
Me
Sister
Brother
Maternal
Aunt
Value of Family History
Guide
management
Inform diagnosis
Family History
Promote risk
assessment
Build rapport
with patients
Family History Collection Tools
Family History Collection Tools
Prenatal Family History and Genetic
Risk Assessment Tool (www.nchpeg.org)
Generate red-flags, risk assessments, a report &
follow-up letter for the provider
Provide decision-support algorithms
Address cultural sensitivity and ethical issues
Promote patient and provider education
Be compatible with electronic health records
Publically available end of 2012
Red Flags
1. Family history of known or suspected genetic
condition
2. Multiple affected family members with same or
related disorders
3. Earlier age at onset of disease than expected
4. Intellectual disability
5. Diagnosis in less-often-affected sex
6. Multifocal or bilateral occurrence in paired organs
Red Flags
7. One or more major malformations
8. Disease in the absence of risk factors or after
preventive measures
9. Abnormalities in growth (growth retardation,
asymmetric growth, excessive growth
10. Recurrent pregnancy losses (2+)
11. Consanguinity (blood relationship of parents)
12. Ethnic predisposition to certain genetic disorders
Red Flags
Cystic Fibrosis
European
Ashkenazi Jewish
Tay-Sachs Disease
Canavan Disease
Cystic Fibrosis
Familial Dysautonomia
Mucolipidosis IV
Niemann-Pick Disease
(Type A)
Fanconi Anemia Group C
Bloom Syndrome
Gaucher disease
Ashkenazi Jewish
Sickle Cell Disease
African
Asian Indian
Middle East
Mediterranean
Alpha-thalassemia
SE Asian
African
Caribbean
Tay-Sachs Disease
Ashkenazi Jewish
French Canadian
Cajun
Pennsylvania Dutch
Beta-thalassemia
Mediterranean
Asian
Middle Eastern
Hispanic
Caribbean
Risk Assessment & Mgt Guidelines
Risk Assessment & Mgt Guidelines
CASE STUDY ONE
Case Study 1 -- Anna
Anna is a healthy 30 year old who presents to
your office for her first prenatal care visit. She
is 10 weeks pregnant. In inquiring about her
family health history, she reveals that her
brother (Harold) possesses an intellectual
disability (ID)*.
*Formerly known as mental retardation or cognitive disability.
Case Study 1 - Anna
Anna’s Family Pedigree
Case Study 1 - Anna
Known Causes* of Intellectual Disability (US)
* The etiology of 75% of all ID cases is unknown.
Most Common
Down Syndrome
Fragile X
Fetal Alcohol
Syndrome (FAS)
Less common
Infections
Birth defects (brain)
Injuries
Untreated metabolic
disorders
Other genetic conditions
Info Sources: CDC & NLM
Case Study 1 - Anna
What “red flags” would you expect to see in the FmHx for…
Fragile X
Down Syndrome
Sporadic,
typically no
family history
Advanced
maternal age
Multiple family
members presenting
w/ID
X linked inheritance
pattern
Female Carriers
FAS
Maternal
Alcohol Use
Primary Ovarian
Insufficiency
Male Carriers
Adult-onset
tremors/ataxia
Info Sources: Nat Institute Child Health
& Dev., Nat Fragile X Foundation,
Case Study 1- Anna
In talking to Anna further you discover:
In addition to Harold (26 yrs), Anna also
has a younger sister Margarite (22 years).
Anna’s mother (Sarah) had all three
children by age 26.
Sarah stopped having her period at age
32.
Sarah does not consume alcohol.
Case Study 1 - Anna
Anna’s Family Pedigree (Updated)
POI - Primary Ovarian Insufficiency
Case Study 1- Anna
Fragile X
Most common inherited
cause of ID
Repeat expansion in the
FMR1 gene
Recessive X-linked
No cure, but therapy
enhances functioning
Phenotypic Expression
ID -Varies substantially
Behavioral issues
Speech/Lang problems
Long face/ears, jaw
Sensory Issues
Boys more severely
affected
Info Sources: NIH, Nat. ACOG
Males more severely
impacted
Photo Credit: Families and Fragile X Syndrome., NICHD
Case Study 1 - Anna
Symptoms of Pre-mutation Carriers
Female
POI (20-22%)
Typically cognitive
functioning is normal
Late onset Fragile X
tremors/ataxia (but
more often in males)
Male
Typically cognitive
functioning is normal
Late onset Fragile X
Tremors/Ataxia
Info Source: ACMG, Nat. Fragile X Foundation
Case Study 1 - Anna
Symptoms of Full-mutation Carriers
Female
No fertility issues
May have Frag. X
physical features
Most have normal
cognitive functioning
More affected by
depression, anxiety
Male
Display Fragile X
symptoms
Info Source: Nat. Fragile X Foundation
Case Study 1- Anna
What are the next steps?
Offer
genetic testing for FMR-1 for Anna and Harold
(ACOG Committee on Genetics Opinion #469)
Referral to genetic counseling (ACOG Committee on
Genetics Opinion #469)
Assess Anna’s anxiety level
Case Study 1 - Anna
Anna and Harold’s test results are back…
Harold tests positive for Fragile X
Anna is a full-mutation Fragile X carrier
An ultrasound reveals that Anna is carrying a girl
Case Study 1 - Anna
So what are the future implications…
Anna – as a full mutation carrier
Anna’s daughter
Early & regular developmental assessment
Future pregnancies
Most likely will not face infertility issues
May experience cognitive functioning decline
More likely to be affected by anxiety/depression
Female - 50% risk for being full mutation Fragile X carrier
Male - 50% risk for being affected by Fragile X
Discussion of reproductive options
Anna’s sister Margarite
Suggest Anna speak w/Margarite about test results
CASE STUDY TWO
Case Study 2 -- Soledad
Soledad and her husband Robert, an American soldier,
present to your office for a preconceptional care visit.
Soledad and Robert are both 28 years old. Soledad grew
up in Mexico and she and Robert moved to the community
about 6 months ago due to Robert’s assignment to the local
military base. Soledad's primary language is Spanish and she
requires translation, which is provided by Robert, during the
visit. The couple is thinking about trying to conceive again,
however they are apprehensive since three years ago they
lost their first baby due to complications associated with an
“opening in her spine.”
Case Study 2 – Soledad
Spina Bifida
Most common Neural Tube Defect
Symptoms/complications vary
NT forms 28 days after conception
Tube fails to close around the spine
1500 US babies affected per year
No/Minor physical problems to
severe physical and intellectual
disabilities
Treatment may include:
Surgery
Physiotherapy
Assistive equipment
Picture Credit: CDC
Sources: CDC, ACOG , Nat Institute for
Neurological Disorders and Stroke
Case Study 2 - Soledad
Complex condition influenced by environment & genes
Insufficient maternal folic acid intake
Insufficient maternal folic acid metabolism
Uncontrolled maternal diabetes
Maternal obesity
Excessive maternal alcohol use
High maternal core body temperature
Accutane use
Chromosomal disorders, particularly Trisomy13 & 18
Higher risk populations
4% risk if 1 previous NTD birth OR if parent has an NTD
10% risk if 2 previous NTD births
Hispanics and Caucasians
Source: ACOG, MA Batshaw:
“Children with Disabilities.”
Case Study 2 - Soledad
With Respect to Soledad and Robert’s family health
history, what “Red Flags” do you see?
Previous affected child
Ethnic predisposition (Hispanic ethnicity)
Case Study 2- Soledad
What are the next steps?
High dose (4 mg) folic acid (ACOG Bulletin #44)
Nutrition counseling (healthy balanced diet), consider
nutritionist referral
Genetic counseling referral
Obtain records for previous baby
Cultural Competency aspects
Connect Soledad with bilingual staff person in your office
and/or an available interpreter service
Assess patient preferences for bilingual provider or
interpreter services for nutrition & genetic counseling visits
Case Study 2 - Soledad
So what are the future implications…
Risk for future pregnancy
Next pregnancy: 4% risk of having a second child with NTD
If she has another affected baby, risk increases to 10%
Critical prevention steps
Folate-enriched diet
Periconceptional folic acid supplementation (4 mg)
Prenatal screening & diagnostic testing
Maternal serum alpha-fetoprotein test
Anatomic ultrasound
Possibly amniocentesis
Source: ACOG
CASE STUDY THREE
Case Study 3 - Keisha
Keisha is a 34 years old African-American woman
who presents to your office for prenatal care. She
is accompanied by her husband Shawn, who is also
34 years old and African-American. Keisha is 10
weeks pregnant. This pregnancy was unplanned.
This is the couple’s first child, however Keisha has a
son, Eric (5 yrs), from a previous marriage.
Case Study 3- Keisha
Keisha painstakingly relates the story of receiving a
call from Eric’s doctor that his heel stick test
screened positive for sickle cell disease. Follow up
testing confirmed that Eric had sickle cell disease.
Keisha recounts her shock and dismay surrounding
Eric’s diagnosis as she thought the disease had been
cured. The family has endured many social,
emotional, and financial hardships since Eric’s
diagnosis. Keisha also describes feeling helpless
during Eric’s frequent pain crises.
Case Study 3 - Keisha
Sickle Cell Disease
Mutation in the hemoglobin-Beta gene causes red
blood cells to take on a sickle shape due to a
decrease in oxygen
Effects 70,000-100,000 individuals in the US
Frequent Complications/Symptoms
Sickle
cells “clog” blood vessels which can lead to pain,
organ damage, & increased susceptibility to infection
Anemia due to shortened lifespan of red blood cells
that have sickled
Source: Nat. Heart, Lung, Blood
Phenotypic expression varies
Institute & Nat. Human Genome
Research Institute
Case Study 3 - Keisha
Sickle Cell Disease (Cont)
Limited success with blood & marrow stem cell
transplants
Treatment to relieve symptoms/complications
Pain
mgt
Blood transfusions
Prophylactic antibiotics (2 months-5 yrs)
Vaccinations for flu/pneumococcus/hepatitis/meningitis
Routine eye check ups by an ophthalmologist
Head ultrasounds to detect stroke risk (children)
Source: Nat. Heart, Lung, & Blood Institute
Case Study 3 - Keisha
Sickle Cell Disease (Cont)
Autosomal recessive inheritance
Included in all state newborn screening panels
Sickle Cell Trait
Carrier for sickle cell disease
Generally no phenotypic expression
Can combine w/other traits & cause other sickling disorders
> 2 million Americans have sickle cell trait
About 1 in 12 African Americans
About 1 in a 100 Hispanic-Americans
Source: Nat. Heart, Lung, Blood
Institute ; Nat Human Genome
Research Institute; SACHDNC
Case Study 3 - Keisha
What red flags do you see in Keisha’s family
history?
Family history of sickle cell disease
Keisha
has sickle cell trait
Eric has sickle cell disease
High Risk Ethnicity (African-American)
Case Study 3 - Keisha
So what is the next step?
Carrier testing of Shawn -- CBC and Hemoglobin electrophoresis
(Source: ACOG Bulletin #78)
Insurance Considerations
Coverage of carrier testing for
asymptomatic
Lack of insurance
Fear of losing insurance or job
if test confirms sickle cell trait
Genetic Information
Nondiscrimination Act
(GINA) prevents this
GINA clinician resources
http://www.nchpeg.org
Cultural Considerations
Concern about racial
discrimination
Distrust of medical care &
research systems
Case Study 3 - Keisha
THE DECISION
Keisha and Shawn discuss and decide to have Shawn
tested.
TEST RESULTS
Shawn tests positive for sickle cell trait.
As such, Keisha and Shawn’s baby has:
25% chance of receiving two “normal” genes
50% chance of having sickle cell trait
25% chance of having sickle cell disease
Case Study 3 - Keisha
So what is the next step?
Describe options for prenatal diagnosis
No
prenatal diagnosis
Chorionic Villus Sampling (10-12 weeks gestation)
Amniocentesis (after 15 weeks gestation)
Referral to genetic counseling
Source: ACOG
Practice Bulletin #78
Case Study 3 - Keisha
PRENATAL DIAGNOSIS DECISION
Keisha and Shawn opt to have an amniocentesis.
PRENATAL DIAGNOSIS RESULTS
The baby has sickle cell trait.
Case Study 3 - Keisha
Future Implications
Current pregnancy
The child
Newborn screening education (ACOG Cmt Opinion #481)
Genetic counseling to address implications of sickle cell trait
Future pregnancies
SCA risk is the same for each pregnancy
25% “normal”, 50% sickle cell trait, and 25% sickle cell disease
Genetic counseling about reproductive options (ACOG
Practice Bulletin #78)
If Keisha or Shawn have a different partner, then the
partner should be offered the opportunity to be screened
for sickle cell trait (ACOG, Practice Bulletin #78)
Within your practice…
What opportunities exist to support the use
of Family Health History (FmHx)?
Overcoming the “time” issue
Building skills in collecting and analyzing FmHx
Keeping FmHx easily available & current
Using FmHx to develop risk assessment & care plans
Linking w/local genetic professionals
Reimbursement for FmHx
THANK YOU!
