genetics 101 for internists
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MOD Mission
The mission of the March of Dimes is to improve the
health of babies by preventing birth defects, preterm
birth, and infant mortality.
The March of Dimes carries out its mission through
programs of research, community services, advocacy and
education.
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MOD Prematurity Campaign
2003 - 2007Why Prematurity?
Since 1981, the preterm birth rate in the US has
increased nearly 29%.
In 2001, prematurity rose to 11.9% --
the highest ever reported.
There are dramatic racial/ethnic disparities in
premature births
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Prematurity Campaign Goals
To decrease premature birth in the U.S. by 15%
To increase public awareness of the problems ofprematurity
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GeneticsGeneral genetic principals
Cells, genes, chromosomes, DNA
What is a genetic counselor?
Examples
Pediatric: Down syndrome, Fragile X, Prader willi,Williams syndrome
OB: The burden of choice
Adult: Hereditary cancer, Huntingtons disease
Ethical issues
Prevention
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Genetics:
The Science of Heredity
Heredity is the transmission of genetic or physicaltraits from parent to child.
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Gregor Mendel
Austrian Monk
Considered the Father of Heredity
He conducted plant breedingexperiments in their monasterygarden.
In 1865 he made his work public,units of inheritance.
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Biology Review
The body is made up of billions
of cells
The entire human genome is in
every cell
25,000 genes -recipes or
directions to construct a human
Genes are written in thelanguage of DNA
(Deoxyribonucleic acid)
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Normal Male46,XY
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Genetic AnalogyGenome - all of the directions necessary to
make a species
Entire set of cookbooks
Chromosome Single volume of a cookbook
Gene One recipe in a cookbook
Functionally related genes are not necessarily
found close together on a chromosome
Recipes with similar foods are not necessarily
found in the same cookbook
DNA Letters
Mutation in a gene Spelling or typographical error in a recipe
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What is a genetic counselor?
A health care professional with a specialized graduate degreeand experience in medical genetics and counseling
Genetic counselors work as members of a health care team,providing information and support to families:
who have members with birth defects and genetic disorders
or
may be at risk for a variety of inherited conditions
They are trained to provide supportive counseling to families ina non-directive way
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What does a Genetic
Counseling Session Entail?
Family history
Discussion of medical/genetic
problems in general terms
Discussion of risk or
intervention that is specific for
that patient
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Case Examples:
Pediatric Genetics
Down syndrome
Fragile X
Prader Willi
Williams syndrome
People with these disorders
Are living much longer now
Often need adult care/supervision
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Down syndrome
Most common chromosome disorder
Extra 21 chromosome
Prevalence: 1:800 births
350,000 people in USA
Seen in Genetics if:
Features of Down syndrome
High risk in pregnancy
Monitored for health problems
associated with Down syndrome
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Down syndrome
Syndrome: group of symptoms withthe same cause
Mental retardation
Characteristic facial and body
features Heart defects
Vision/hearing problems
Low thyroid
Leukemia
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Down syndromeOutlook
Special schools
Many live semi-independent lives
Marriage/children
Fulfilling lives
Alzheimer disease
Life expectancy: 55 years
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Fragile X SyndromeMost common cause of inherited
mental impairment
Caused by expanding area of DNA onchromosome X
causes a gene on chromosome
X not to workUsually only affects men:XY
Women:XX - are usually carriers
Prevalence:
1 in 4000 males
1 in 6000 females
All races and ethnic groups
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Fragile X Syndrome
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Fragile X SyndromeMental impairment:
Subtle learning disabilities andnormal IQ, to severe mentalretardation
Attention deficit and hyperactivity
Anxiety and unstable mood Autistic behaviors
Characteristic appearance in males
Large head
Long face
Prominent forehead and chin
Protruding ears
Flat feet
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Adults with Fragile X Joint laxity, especially fingers
Large testes (post puberty)
Seizures: 25%
Psychiatric issues continue, anxiety, panic disorder, OCD
Often in residential/occupational programs.
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Adult Premutation carriers Fragile X associated primary ovarian insufficiency (FXPOI)
occurs in at least 22% of premutation carriers.
elevated FSH levels, infertility, premature ovarian failure
(complete cessation of periods before 40) or early
menopause.
In untested women who have sporadic ovarian insufficiencyapproximately 2-7 % have an FMR1 premutation and in thosewith other relatives with ovarian insufficiency the FMR1
premutation incidence is 10-15%.
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Adult premutation carriers Symptoms of FXTAS, a progressive
neurodegenerative condition, occur in at least 1/3of adult (>50 years) male and approximately 5-8%of female premutation carriers.
Symptoms of FXTAS include intention tremor,ataxia, memory loss, dementia, personalitychange including irritability and mood swings andit is often misdiagnosed as Parkinsons,Alzheimers, other ataxias, Multiple Sclerosis, orstroke.
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Prader Willi Syndrome
Abnormality of 15q11.2-q13
Usually deletion
Most common genetic cause of obesity
Prevalence: 1:12,000
750 cases in NYC
both sexes, all races
A very common referral for genetics in NYC hospitals
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Prader Willi characteristicsWeek muscles/feeding difficulties as
infants
Decreased movement
Weak cry, poor reflexes, poor
suck
Excessive eating in early childhood Due to dysfunction in
hypothalamus - lack of satiety
Urge to eat is physiological and
totally overwhelming
Burn less calories - low muscle
mass and inactivity Gradual development of
morbid obesity
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Prader Willi characteristics
Borderline to moderate mental retardation
Delayed gross motor milestones, language
Distinctive behaviors
Temper tantrums, stubbornness
Controlling behavior, obsessive-compulsive
Good at puzzles
Short stature/ small hands and feet
Hypogonadism
Small penis, hypoplastic scrotum
Small labia minora and clitoris
Incomplete pubertal development
Infertility in vast majority
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Adults with PWS Obesity with food seeking behavior
Severe delays in adaptive behavior
Preservative/repetative behaviors
Limited speech
Life expectancy is good if weight is controlled (foodrestriction and behavior management)
People with PWS may have unusual reactions to standarddosages of medications and anesthetic agents. Use extremecaution in giving medications that may cause sedation:prolonged and exaggerated responses have been reported.
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Williams syndromeUsually caused by new deletion onchromosome 7
Prevalence: 1:20,000 births
Cocktail personality
Children more interested intalking to adults than peers
Unafraid of strangers
Inappropriate behavior
Strong expressive languageskills
Very polite Attention deficit disorder
Generalized anxiety
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Williams syndromeFacial features: Broad brow,periorbital fullness, short nose, fullnasal tip, long philtrum, wide mouth,small jaw, and prominent earlobes.Children have full cheeks and small,widely spaced teeth
Mental retardation in most (not all) Ranges from severe to mild
Unique cognitive profile(independent of IQ)
Strengths in auditory rotememory and language
Extreme weakness in
visuospatial construction75% have Supravalvar aortic stenosis
Hoarse voice
Short stature
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Adults with WilliamsAnxiety, depression, other emotional concerns
Diabetes
Endocrine
Gastro-intestinal disorders
ENT/Audiologic
Dental
Accelerated aging appears to be characteristic (may berelated to elastin deletion).
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Case Examples: OB GeneticsWomen are at increased risk to have
a child with a genetic disorder/ birthdefect
Advanced maternal age
Family history medical
problem/genetic disease Exposure to drugs, alcohol,
medication
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Maternal Age Effect
As the age of the motherincreases, the chance for her tohave a child with a chromosome
anomaly slightlyincreases
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More severe than Down syndrome
Severe MR
Will never walk or talk
Many Organ problems
Heart, lung, stomach, kidneys, etc.
Most do not live for more than 1 month
T18
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Paternal Age Effect Age 40+ at conception
DOMINANT mutations, 4-5 times greater than youngerpopulation.
Examples of new Dominant mutations: Achondroplasia,Osteogenesis Imperfecta, Neurofibromatosis
Not diseases that we can check for
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Ethical Issues in Genetics
The Burden of Choice:
Some have a black and whiteopinion regarding having apregnancy with a geneticanomaly
For others: The choice can beunbearable
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Case Examples:
Adult GeneticsHuntingtonsdisease
Hereditary Breast
and OvarianCancer
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Case 1: Huntingtons Disease
John (21 years old) is referred for geneticcounseling because his mother (47 years old) wasrecently diagnosed with Huntingtons disease.
His mother lives in Vancouver and has just receivedher genetic testing results confirming thisdiagnosis.
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Family Tree
Huntingtons Disease
= Affected
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What is HD?Degenerative brain disorder
Symptoms usually between 30 and 50
Death 15-20 years after onset
Symptoms are both
behavioral/emotional as well asphysical
Involuntary movements, drunken
gait
Depression, irritability, aggressive
outbursts, social withdrawal, shortterm memory loss
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Genetic Counseling Appointment
Review features of Huntingtons disease
Review genetics of HD
Autosomal Dominant inheritance
Anticipation
Complete penetrance
No cure or treatment for HDReview testing options including risks and benefits
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Genetic Testing
Pros
Decreased anxiety orworry from not knowing
Make life plans
Cons
Emotional Impact
Increased anxiety orworry if positive testresult
Insurance andemployment issues
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Hereditary Breast and
Ovarian Cancer (HBOC)
Mary is a 48 year old woman who is referred forgenetic counseling because her sister wasrecently diagnosed with ovarian cancer at age 52.
Her father and paternal grand-mother were alsodiagnosed with breast cancer at ages 58 and 45respectively.
Mary tells you her sister has a mutation in the BRCA2gene.
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Family Tree
Hereditary Breast/Ovarian
Cancer
= Affected
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Hereditary Breast and
Ovarian Cancer
Breast cancer 50-85% (9% population risk)
Ovarian cancer 10-40% (1.5% populationrisk)
Men at risk for breast, pancreatic andprostate
Options exist for prevention, early diagnosisand treatment - risks can be reduced forbreast and ovarian cancer by up to 90%
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Genetic Counseling Appointment
Review features of HBOC
Review genetics of HBOC
Autosomal dominant inheritance
Reduced penetrance
Review cancer risks and management options toreduce those risks
Discuss option of genetic testing including risks andbenefits
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Genetic TestingPros
Decreased anxiety orworry from not knowing
Prevent cancer
Increased screening
Medication
Surgery
Cons
Emotional Impact
Increased anxiety or
worry if positive testresult
Insurance andemployment issues
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Ethical Issues in Genetics
Genetic testing onChildren
Who owns geneticinformation?
Patient vs. family
Huntingtons Disease
= Affected
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When to refer to Genetics 2 or more in family diagnosed with breast cancer
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Questions
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Acknowledgements
This presentation was created anddonated to the March of Dimes by:
Christina Barr, MS, CGC, genetic
counselor and former Genetics & YourPractice presenter
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Thank you!
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March of DimesGreater New York Chapter
515 Madison Avenue, 20th Fl.
New York, NY 10022
Tel: 212.353.8353
Fax: 212.254.3518
http://www.marchofdimes.com/greaternewyork/
For more information contact:
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