Download outline6441 - American Academy of Optometry

I.
II.
Paradigm shift: The “old genetics” vs. the “New Genetics”
Learn to use family history as a screening tool.
A. All clinicians take family histories.
B. Because of the genomics revolution, the purpose & scope of taking a FHx have changed.
C. Increased understanding of role of genetics in health means that you need to expand your FHx to
include info on genetic factors.
D. Risk factors for disease
1. Genes, environment, & behaviors interact with each other to cause disease.
2. Family history helps capture the effects of these interactions on disease risk.
E. An efficient, accurate family history can be used to:
1. Develop a differential diagnosis
2. Make a diagnosis
3. Distinguish genetic from other risk factors
4. Identify patterns of inheritance
5. Identify medical risks for other relatives
6. Calculate risks
7. Decide an approach to genetic testing (e.g., whom to test, which type of test to order)
8. Make decisions on management, prevention, & surveillance
9. Assess reproductive options
10. Develop patient rapport and trust
11. See family dynamics (e.g., sources of conflict and support)
12. Educate patients & families; clarify misconceptions
F. The family history is often the first way to identify patients who may benefit from genetic testing,
preventive measures, monitoring, and/or referral.
G. As the standard of care changes, you may be liable legally. Court cases have already occurred where
health care providers were taken to court for neglect for not identifying patients who were at risk for
inherited disorders.
H. In select cases, the FHx info should be converted into a diagram of the biological relationships of your
px with his or her family members – a pedigree.
I.
A pedigree is indicated where:
1. The patient presents with a concern about an inherited disease
2. The patient presents for a routine screening. The patient could fill out a FHx questionnaire.
3. The patient with an established diagnosis of a disease that possibly has a genetic basis
4. The patient indicates a significant family history of an ocular disease or a systemic disease with
an ocular component.
J. Learn how to take a minimum of a three-generation pedigree in selected patients. Maintain and
update the pedigree in these patients.
K. Glaucoma
1. Life-time risk of glaucoma in:
a. Relatives of pxs with glaucoma = 22%
b. Relatives of normal controls = 2.3%
c. (Rotterdam study; Wolfs et al., 1998)
2. Prevalence of:
a. OAG among relatives of pxs = 10%
b. Probable OAG among relatives = 13%
(Barbados Study; Nemesure et al., 2001)
3. Up to 50% of people with glaucoma have a positive FH.
4. For OAG pxs, risk of OAG developing:
a. In siblings = 65%
b. Children = 13%
c. Other relatives = 22%
(Nguyen RL et al., 2000)
5. FH of glaucoma is a very important risk factor for POAG
6. Clinical point: Chase the Family!
a. Relatives of pxs with glaucoma have a strongly increased risk of glaucoma.
b. Immediate & other relatives should be evaluated for glaucoma.
L. Family History Tools
1. Jointly designed tool by the American Society of Human Genetics, the Genetic Alliance, and the
National Society of Genetic Counselors. The px accesses tool online, fills it out, & brings to office
2. Pamphlet: “Family Medical History in Disease Prevention”: available at AMA web site
1
3.
III.
IV.
V.
March of Dimes clinical genetics program
a. Excellent web site
b. Contains sections on Genetic testing & screening, Family Health and Social History, &
Referral to Genetic Services
4. Book: “The Practical Guide to the Genetic Family History” by R.L. Bennett
5. U.S. Surgeon General’s Family History Initiative. Goals include:
a. Increase the public’s awareness of the importance of FHx in health.
b. Give the public tools to gather, understand, evaluate, & use FHx to improve their health.
c. Increase the awareness of health professionals about the importance of FHx.
d. Give health professionals tools to gather, evaluate, and use FHx information.
Learn to recognize the genetic flags (using the Family GENES pneumonic).
A. F – Family history
1. Look for multiple affected siblings or individuals in multiple generations.
B. G – Groups of congenital anomalies
1. Two or more anomalies are much more likely to indicate the presence of a syndrome with genetic
implications.
2. Look for the presence of any other anomaly in an individual with a common, multifactorial
malformation.
C. E – Extreme or exceptional presentation of common conditions
1. Look for a common disorder with an earlier age of onset than typical (especially in multiple family
members). Some examples include:
a. Vision loss: < age 55 years
b. Corneal arcus: < age 50 years
c. Hearing loss: < age 50-60 years
d. Heart disease: < age 40-60 years
2. Look for unusually severe reaction to infectious or metabolic stress.
D. N – Neurologic symptoms including developmental delay
E. E – Extreme or unusual pathology
1. Bilaterality of pathologic findings in paired organs or structures (e.g., retinoblastoma in both eyes
is an indication that the patient has inherited a mutation in the RB1 gene).
2. Appearance of multiple primary neoplasms (e.g., multifocal sites of retinoblastoma).
3. Rare physical finding like congenital hypertrophic retinal pigment epithelium (CHRPE) may be
associated with familial adenomatous polyposis (FAP).
F. S – Surprising laboratory values
1. Abnormal lab values in an otherwise healthy patient may be a clue to a genetic disease (e.g.,
high cholesterol in familial hypercholesterolemia or high serum transferring saturation or ferritin
levels in hereditary hemochromatosis).
2. Extreme lab values for a typical clinical situation may also be a red flag.
Assume all disorders have a genetic component.
A. Essentially all disorders (except possibly trauma) have a genetic component.
B. Common systemic disorders that have genetic components include: Type 1 and Type 2 diabetes,
hypertension, heart disease, asthma, cancers, and Alzheimer disease.
C. Common ocular disorders that have genetic components include: ARMD, the glaucomas, cataracts,
myopia, and diabetic retinopathy.
D. The more common diseases are multifactorial in that they involve multiple genes interacting with
environmental influences.
E. Expand your differential diagnosis to include genetic disorders.
F. Set a low threshold for genetic hypotheses.
G. Try to develop a unifying hypothesis for disparate findings.
H. Learn to “think genetically.”
I.
Look at your patients through a new genetic/developmental/environmental lens.
Learn the genetics of the disorders you see most often in your practice.
A. Tremendous advance in knowledge of genetics of common ophthalmic disorders
B. As more and more is discovered:
1. More diagnostic tests will become available
2. You will have more information to:
a. Help your pxs understand their conditions
b. Help them make decisions
c. Provide supportive counseling
2
C.
VI.
VII.
VIII.
IX.
Excellent reviews are available on the genetics of: Age-related macular degeneration, Cataracts,
Corneal dystrophies, Glaucomas, Myopia, Neuro-ophthalmic disorders, & Retinal dystrophies.
D. Example: the genetics of the glaucomas.
E. Look for clues in the presentation and setting.
Learn how to appropriately order and interpret selected genetic tests.
A. In the future, the number & availability of genetic tests for ocular conditions will increase. The pressure
to use these tests will increase.
B. Become familiar with the GeneTests web site.
1. Identify labs that offer specific genetic tests
2. Identify research labs that may provide opportunities for your px to be a research subject
C. GeneTests web site offers GeneReviews (Online publication of expert-authored disease reviews), a
Laboratory Directory, a Clinic Directory, Educational materials, & it is searchable by disease name,
clinical disease feature, location, laboratory, etc.
D. PubMed is an excellent source for articles on particular conditions
(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed)
1. Gives you info on the condition
2. Allows you to identify researchers whom you can contact
E. Glaucoma and the OcuGene Test: Should you use this test or not?
Learn how genes flow through populations and how this influences individual risk.
A. The risk of a specific disease may be greatly increased in a specific population or ethnic group. This
may warrant screening in patients of that population.
B. Prevalence of OAG (40 years & older)
1. Whites
1-2%
2. Latinos
5%
3. Blacks
3-9%
C. Part of the differences in prevalence are due to genetic differences.
D. Learn the characteristics of:
1. Chromosomal disorders
2. Monogenic disorders (autosomal dominant, autosomal recessive, X-linked, mitochondrial)
3. Multifactorial disorders
E. Allows you to recognize inheritance patterns via FHx & pedigree analysis.
F. Examples include screening for Tay-Sachs disease in Ashkenazi Jewish patients or sickle cell trait or
disease in patients with African, Southeast Asian, or Mediterranean ancestry, or congenital glaucoma
in an Amish population.
G. Learn the characteristics of autosomal dominant, autosomal recessive, X-linked, and mitochondrial
inheritance patterns.
H. Learn the characteristics of complex (multifactorial) disorders.
Develop a referral network for genetic conditions.
A. Identify the genetic professional in your area
B. Establish an ongoing relationship with one or more of these professionals
C. Learn how to refer pxs to these professionals
D. Seek advice from them as you begin to acquire competency
E. Find a genetic counselor in your area using web site of the National Society of Genetic Counselors
(http://www.nsgc.org/)
1. Click on “Find a Counselor”
2. Simplest method – Put in: your zip code, indicate within how many miles, & the Area of
Practice/Specialization (“Hearing or visual impairment”).
F. Find a medical geneticist in your area using the web site of the American College of Medical Genetics
(http://www.acmg.net/)
1. Under “ACMG Resources,” click on “Membership Directory”
2. Enter your city and state
G. Identify px support groups for specific conditions using web site of the Genetic Alliance
(http://www.geneticalliance.org).
Learn to recognize the ethical, legal, and social issues raised by genetic diagnosis.
A. Issues of privacy & confidentiality
1. Already deal with these
2. Take on greater significance for genetic conditions
3. Genetic info may affect an entire family, not just the px
4. Genetic discoveries may be predictive of future adverse events
5. Genetic info & the choices of the present may affect future generations
3
X.
XI.
B. Learn how to obtain informed consent for genetic testing.
C. Consider possibility of genetic discrimination (e.g. employers and/or insurance companies).
D. May have to deal with conflict between duty to maintain privacy & duty to warn family members of
possible risk
1. Duty to warn based on premise that warning is necessary to avert serious harm
2. Breach of confidentiality rarely justified – except where prevention & Tx is possible
E. Px may experience feelings of stigmatization, guilt/shame, or loss & grief.
F. Genetics issues raise implications for whole family
G. Optometric primary care providers are in a good position to handle genetic conditions. Typically they
know the pxs & their families.
Most importantly, learn how to locate genetic information and resources when you need them.
A. Develop life-long learning skills
B. Learn how to use some of the excellent web-based resources
C. Learn how to use Web-based resources. Examples include:
1. Online Mendelian Inheritance in Man (http://www.ncbi.nlm.nih.gov/omim).
2. GeneClinics (http://www.geneclinics.org).
3. National Coalition for Health Professional Education in Genetics (http://www.nchpeg.org).
4. National Human Genome Research Institute (http://www.nhgri.nih.gov).
5. RetNet (Retinal Information Network) (http://www.sph.uth.tmc.edu/Retnet/).
6. Genetics and Your Practice (http://www.marchofdimes.com/gyponline/index.bm2).
7. National Organization for Rare Disorders (http://www.rarediseases.org/).
8. PubMed (http://www.ncbi.nlm.nih.gov/entrez/).
D. Learn how to use selected journals and textbooks for genetic information.
E. Learn how to evaluate the accuracy and validity of Websites, journal, book, and other forms of
information.
F. Knowledge of databases, decision-support tools, and information technology is becoming essential in
clinical practice.
Getting the new genetics into practice.
A. Crucial role players: primary care optometrists, pediatric optometrists, & low-vision optometrists
B. Increased genetics/genomics education in schools & colleges of optometry
C. Increased CE opportunities for practicing optometrists
D. Increase your skills in: case recognition, diagnosis, management, px ed. & referral of genetics cases
E. Establish relationships with colleagues who specialize in genetics
4