genetics 101 for internists

7/30/2019 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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