Genetic Counseling
for Neurogenetic
Conditions
Karen Kovak, M.S., C.G.C.
Child Development & Rehabilitation Center
Shriner’s Hospital
OHSU Cancer Center
Who Should Have a Genetics
Consultation?
Individuals and families who are
concerned about a genetic disease
may benefit from a genetic
consultation whether or not
testing is available for that
condition. Many people are
seeking information and coping
strategies as much as test results.
Genetic Counseling as a
Profession
Genetic counseling is the process of helping people understand and
adapt to the medical, psychological and familial implications of
genetic contributions to disease. This process integrates the
following:
 Interpretation of family and medical histories to assess the chance of
disease occurrence or recurrence.
 Education about inheritance, testing, management, prevention,
resources and research.
 Counseling to promote informed choices and adaptation to the risk
or condition.
Genetic counseling needs vary depending on the context of the
disorder in the family and the complexity of the disorder/testing
options.
Genetics Clinic Evaluation
Family
history
Pregnancy,
Physical
medical, developmental history
exam
Dysmorphology
Diagnostic
exam
evaluations
Genetic
testing
Genetic
counseling
Support
and Information Resources
Clinical Features of Huntington
Disease

Movement Disorder
involuntary movements/chorea
impaired voluntary movements

Psychiatric Disorder
major DSM diagnoses
nonspecific – irritability, apathy, disinhibition

Cognitive Disorder
organization, sequencing
lack of initiation
decreased insight/unawareness
learning/memory
Age of Onset in Huntington
Disease



Range
2-28 years
average around 40 years
Juvenile Onset
defined as <21 years
5-10%
Late Onset
defined as >60 years
10%
Milder progression/severity?
Progression of Huntington Disease

Early mild motor & mood impairment
depression/irritability
mild problems with coordination & thinking

Mid

Late assistance with all ADLs
speech & swallowing problems
chorea – falls, weight loss
cognitive impairment leads to inability to work/drive
nonverbal/nonambulatory
chorea may decline & rigidity appear
Suicide Risk in early/mid stages
Survival 3-42 years with average 15-20
Huntington Disease Gene
•CAG trinucleotide repeat expansion
•Ranges of repeat size: normal
intermediate
reduced penetrance
affected
•Repeat size does not predict age of onset
•Repeat size instability
Categories of CAG Repeat
Sizes
26 27
35 36
39 40
…CAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG…
Unaffected
“Mutable” Unaffected
“Reduced
Penetrance”
Affected
Repeat may be unstable when larger than 26 repeats
Inheritance of Huntington
Disease
18 22
42 17
17 22
44 18
42 22
Genetic Testing for Huntington
Disease

Diagnostic/Confirmatory
absent family history
early/atypical symptoms & family history but no DNA

Predictive/Presymptomatic
testing in healthy person without symptoms
no medical benefit

Prenatal
parental status – gene status known or not
prenatal vs. preimplantation



Genetic testing may be used for medical
management and personal decisionmaking
Genetic test results usually apply not only to
the patient but also to other family
members
Genetic testing may be performed in the
context of a genetics consultation and
should include informed consent, test
interpretation, and follow-up medical and
psychosocial services
www.geneclinics.org
Genetic Discrimination
Definition
 Analysis of Risk (how big a problem?)
 Fear of discrimination in clinical &
research practice
 Several studies show fear of genetic
discrimination is the most common reason
for declining genetic services
 Legislation

Oregon Genetic Privacy Act 1995:
goal of
protecting individuals from employment and insurance
discrimination on the basis of genetic test results
•HIPAA – Health Insurance Portability &
Accountability Act 1996 (took effect 2003):
1)genetic information shall not be deemed a preexisting condition
and 2)restricts group health plans from using genetic information
to determine insurance eligibility and premiums
•Genetic Information Nondiscrimination Act
of 2005: 1)prohibits discrimination in enrollment &
premiums based on request for or receipt of genetic services and
2)prohibits requiring genetic testing
Diagnostic Testing for HD
Prolonged diagnosis
Focus on prognosis/management
Testing usually done by neurologist
How to contact biologic family
Onset mild chorea at 45
Normal MRI, thyroid, B12, Vit E
Depression/anxiety/memory loss by 50
42 CAGs
Applications for Genetic Testing
?
Diagnostic
testing
Presymptomatic
testing
Prenatal
? testing
= Huntington
disease
Genetic Testing Guidelines

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
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

Genetic Counseling
Results
Support
Psychological Consequences of Testing
Testing Symptomatic Individuals Vs. Nonsymptomatic
Family Issues/Communication
Reproductive Decisions/Options
Genetic Discrimination
Reproduction Options






Natural reproduction without genetic testing
Prenatal testing by amniocentesis or chorionic
villus sampling –disclosing vs. non-disclosing
testing
Egg or sperm donor
Adoption
Surrogate mother
Pre-implantation genetic diagnosis
Most Common Concerns about HD
When will I get HD?
 Is there a cure for HD?
 How severe will my symptoms be?
 How do I tell my children about their risk
and how do I get them tested?

Common risks in Predictive Testing
for Huntington Disease

Negative results are not always a happy
ending
Not
tested
BTL at 25
Tested at 44
4
Risks in Predictive Testing –
survivor guilt & “unplanned future”
?
No symptoms at age 45
Considering career change
6 months after normal test
result, depression requiring
hospitalization
Onset
20s
Youngest child was
17 at time of testing
Risks in Predictive Testing

Unanticipated Results
Patient did not reveal existence of
son until after test results
Son was product of brief
relationship, and was adopted out
through a state agency
35 & 22 CAGs
Risks in Predictive Testing



Bad outcomes may occur regardless of result
Time of risk differs
Risk factors for suicide after testing include:
unemployment
past history of depression
contact with persons with Huntington disease
no children/no partner


Suicide risk is 4-8 times higher than in non-HD population, and is 24 times higher among partners of persons with HD
Risks for depression higher with result discrepant from expectation
Risks in Predictive Testing
2
Onset 30s
Suicide following uncle’s death
Genetic Test Applications
•Prenatal/preimplantation testing
•Diagnostic testing
•Presymptomatic testing
•Predisposition testing
•Carrier testing
•Newborn screening
Predisposition Genetic Testing


Testing of healthy/unaffected persons for a
condition with incomplete penetrance
Examples include:
BRCA1/2 gene mutations
Hemochromatosis

Genetic Counseling needs affected by
availability of interventions, certainty of disease
ELSI: Genetic Testing

Should testing be done for susceptibility genes?

role of environmental factors in disease development

Should parents have the right to have their
minor children tested for adult-onset diseases?

Are current genetic tests reliable and
interpretable by the medical community?
Awareness of Family Health History as
a Risk Factor for Disease
Survey of consumers conducted by the
CDC
 96.3% of respondents considered
knowledge of family history important to
their personal health
 30% reported actively collecting health
information from relatives to develop a
family health history

www.cdc.gov/mmwr/preview MMWR 11/12/04/53(44)
Genetic Tests Differ from Common
Laboratory Tests

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Because most genetic disorders are rare, genetic testing
is often done only by specialized laboratories.
Intense research efforts in molecular genetics result in
the rapid development and availability of new genetic
tests; therefore, healthcare providers need to
continuously update their knowledge.
In order for genetic testing to yield meaningful results:



multiple test methodologies may be required
other family members may need to be tested
a genetics consultation may be appropriate
Charcot- Marie –Tooth Hereditary
Neuropathy



Disease characteristics: Charcot-Marie-Tooth (CMT) hereditary
neuropathy refers to a group of disorders characterized by a chronic
motor and sensory polyneuropathy. The affected individual typically
has distal muscle weakness and atrophy often associated with mild
to moderate sensory loss, depressed tendon reflexes, and higharched feet. The CMT hereditary neuropathies are categorized by
mode of inheritance and causative gene or chromosomal locus.
20 years ago, known by mode of inheritance
Currently: autosomal recessive - 7 genes
autosomal dominant - type 1 with >4 genes
type 2 with>6 genes
X-linked - >2 genes
www.geneclinics.org; author Tom Bird, M.D.
Family History of CMT
Possible symptoms
No insurance
?
Should kids be tested?
8 yr.
Who decides?
No symptoms
What test?
3 yr.
toe-walker
CMT Gene Locations
Duchenne/Becker Muscular
Dystrophy

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X-linked
Cause may be family mutation, new mutation, or gonadal
mosaicism
Caused by mutations in dystrophin gene
Gene testing can involve multiple steps:
2/3 have large deletion in dystrophin gene
5-10% have point mutation
5-10% may have duplication
rest unknown?
DNA testing often obviates need for muscle biopsy
New health issues for female carriers
Duchenne/Becker Muscular
Dystrophy
Counseling Issues:
Who is at risk
Prenatal testing
available?
6
4
2
1) no deletion
2) sequencing normal
3) duplication testing not available clinically
p
What will happen to genetic testing
over the next decade?
Dr. Francis Collins www.genome.gov, A Brief Primer on Genetic Testing


Major genetic factors involved in susceptibility
to common diseases like diabetes, heart
disease, Alzheimer’s disease, cancer, and
mental illness will be uncovered in the next 5-7
years
“It will be important to remember, however, that
most of these tests will not be “yes” or “no”
but rather will predict relative risk”