Ben Siegel, MD
Professor of Pediatrics and Psychiatry, Boston
University School of Medicine
I have nothing to disclose
Objectives:
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To place the ethical and policy issues for genetic
testing and screening into the practice of
primary care pediatrics: complexity of health and
illness
To discuss what screening we do now for
primary, secondary and tertiary prevention and
treatment
To focus on newborn universal screen as the
basis for discussion of ethics and public policy as
a framework for the discussion by Drs Kahn and
Wang
Challenges
•Health
and Illness are only understood as very
complex interaction between genes and the
environment (psychosocial, political legal economic)
•Newborn Screening is universal (4 million children
each year)
•Many tests are mandated by law
•The diseases detected are rare and associated with a
single biochemical marker
• How does this technology translate into the rest of
medicine?
Ecobiodevelopmental Framework
Ecobiodevelopmental Framework
Shonkoff J. and Garner, A Pediatrics: 2012;129:e232-e246
Shonkoff, J. and Garner, A. Pediatrics: 2012;129:e232-e246
Newborn Screening Tests
The diseases are rare:
a. Inborn Errors of Metabolism
b. Endocrine
c. Hemoglobinopathies
d. Perinatal infectious Diseases
The screening tests are very specific, based on
mostly single or simple biochemical markers
Frequency in the population: 1:2400-1:6000 live
births
• 30 are standard screens all states by Law
• 25 additional and optional: require informed
consent
•
Science of Screening
Newer Technologies
1. Radioimmunoassay
2. Polymerase chain reaction (PCR)
3. Tandem mass spectrometry
Characteristics of a Good
Screening System
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The disease has significant morbidity or
mortality
The treatment is safe and effective
Screening is reliable with low false negative rates
The tests are simple and inexpensive
The results are timely so that the disease is not
symptomatic and intervention is possible
For the newborn: the follow up confirmatory
tests identify the true positives and rule out the
false positives
Problems with screening
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Some tests are not sensitive (the test identifies all
who are at risk in the population). E.G. Cystic
Fibrosis, more than 1500 mutations in CFTR
causing cystic fibrosis. The screening test picks up
only about 80% of all positive newborns.
The psychological stress if a test Is positive and
the time it takes to make a definitive diagnosis
Costs of screening and of treatment
Not all states provide all of the same tests
Secondary conditions as of 1/6/13
O Required by law and implemented A offered but not required B offered to
select populations D Likely to be detected as a by product of Mass Spectrometry
Severe Combined Immune-Deficiency (July 2011)
Problems with the Future: DNA
analysis
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3.
Epigenetic change — A modification of a
chromosome that does not alter the DNA base
sequence, but alters the expression of a gene. May be
passed on to offspring. Usually caused by geneenvironment interaction
Expressivity —quantifies the degree to which an
inherited characteristic is expressed in an organism:
Variation of Symptoms (e.g. CF)
Penetrance —probability that an individual harboring
a disease-causing genotype will develop the associated
disease or condition. Incomplete penetrance occurs
when an individual with a disease-causing genotype
does not manifest features of the disorder
Type 2 Diabetes: Heritability
about 26%
Environment contribution about 74%
1. Obesity
2. Physical inactivity
3. Having a parent with gestational diabetes
4. High Blood pressure ( added stress)
5. Elevated cholesterol
6. Hx. of cardiovascular diseases
Uncertainty and complexity in the
future: What does one do with the
results of DNA sequencing?
Ethical and Policy Conundrum and
Challenges
Gene Environmental Interaction:
Potential Epigenetic Changes
Impacting Future Generations
Only if time
Adverse Childhood Events (ACE)
http://www.cdc.gov/ace
Relationship of Childhood Abuse and Household
Dysfunction to Many of the Leading Causes of Death
in Adults
Felitti V. et al. Amer. Jo. of Prev. Med. 1998;14:245
Adverse Childhood Events