Genetics 101

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.

MOD Prematurity Campaign 2003 - 2007

Why 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

Prematurity Campaign Goals

To decrease premature birth in the U.S. by 15%

To increase public awareness of the problems of prematurity

Genetics
General 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

Genetics: The Science of Heredity

Heredity is the transmission of genetic or physical traits from parent to child.

Gregor Mendel
Austrian Monk Considered the Father of Heredity He conducted plant breeding experiments in their monastery garden. In 1865 he made his work public, units of inheritance.

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 the language of DNA (Deoxyribonucleic acid)

Normal Male 46,XY

Genetic Analogy
Genome - 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
Mutation in a gene

Letters
Spelling or typographical error in a recipe

What is a genetic counselor?

A health care professional with a specialized graduate degree and 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 in a non-directive way

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

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

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

Down syndrome
Syndrome: group of symptoms with the same cause Mental retardation Characteristic facial and body features Heart defects Vision/hearing problems Low thyroid Leukemia

Down syndrome
Outlook Special schools Many live semiindependent lives Marriage/children Fulfilling lives Alzheimer disease Life expectancy: 55 years

Fragile X Syndrome
Most common cause of inherited mental impairment Caused by expanding area of DNA on chromosome X causes a gene on chromosome X not to work Usually only affects men:XY Women:XX - are usually carriers Prevalence: 1 in 4000 males 1 in 6000 females All races and ethnic groups

Fragile X Syndrome

Fragile X Syndrome
Mental impairment: Subtle learning disabilities and normal IQ, to severe mental retardation 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

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.

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 insufficiency approximately 2-7 % have an FMR1 premutation and in those with other relatives with ovarian insufficiency the FMR1 premutation incidence is 10-15%.

Adult premutation carriers

Symptoms of FXTAS, a progressive neurodegenerative condition, occur in at least 1/3 of adult (>50 years) male and approximately 5-8% of female premutation carriers. Symptoms of FXTAS include intention tremor, ataxia, memory loss, dementia, personality change including irritability and mood swings and it is often misdiagnosed as Parkinsons, Alzheimers, other ataxias, Multiple Sclerosis, or stroke.

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

Prader Willi characteristics

Week 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

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

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 (food restriction and behavior management)
People with PWS may have unusual reactions to standard dosages of medications and anesthetic agents. Use extreme caution in giving medications that may cause sedation: prolonged and exaggerated responses have been reported.

Williams syndrome
Usually caused by new deletion on chromosome 7 Prevalence: 1:20,000 births Cocktail personality Children more interested in talking to adults than peers Unafraid of strangers Inappropriate behavior Strong expressive language skills Very polite Attention deficit disorder Generalized anxiety

Williams syndrome
Facial features: Broad brow, periorbital fullness, short nose, full nasal 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 rote memory and language Extreme weakness in visuospatial construction 75% have Supravalvar aortic stenosis Hoarse voice Short stature

Adults with Williams

Anxiety, depression, other emotional concerns Diabetes Endocrine Gastro-intestinal disorders ENT/Audiologic Dental Accelerated aging appears to be characteristic (may be related to elastin deletion).

Case Examples: OB Genetics

Women are at increased risk to have a child with a genetic disorder/ birth defect Advanced maternal age Family history medical problem/genetic disease Exposure to drugs, alcohol, medication

Maternal Age Effect

As the age of the mother increases, the chance for her to have a child with a chromosome anomaly slightly increases

T18

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

Paternal Age Effect

Age 40+ at conception DOMINANT mutations, 4-5 times greater than younger population.

Examples of new Dominant mutations: Achondroplasia, Osteogenesis Imperfecta, Neurofibromatosis

Not diseases that we can check for

Ethical Issues in Genetics

The Burden of Choice:
Some have a black and white opinion regarding having a pregnancy with a genetic anomaly For others: The choice can be unbearable

Case Examples: Adult Genetics

Huntingtons disease Hereditary Breast and Ovarian Cancer

Case 1: Huntingtons Disease

John (21 years old) is referred for genetic counseling because his mother (47 years old) was recently diagnosed with Huntingtons disease. His mother lives in Vancouver and has just received her genetic testing results confirming this diagnosis.

Family Tree
Huntingtons Disease

= Affected

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 as physical Involuntary movements, drunken gait Depression, irritability, aggressive outbursts, social withdrawal, short term memory loss

Genetic Counseling Appointment

Review features of Huntingtons disease Review genetics of HD Autosomal Dominant inheritance Anticipation Complete penetrance No cure or treatment for HD Review testing options including risks and benefits

Genetic Testing
Pros Decreased anxiety or worry from not knowing Make life plans

Cons Emotional Impact Increased anxiety or worry if positive test result Insurance and employment issues

Hereditary Breast and Ovarian Cancer (HBOC)

Mary is a 48 year old woman who is referred for genetic counseling because her sister was recently diagnosed with ovarian cancer at age 52. Her father and paternal grand-mother were also diagnosed with breast cancer at ages 58 and 45 respectively.
Mary tells you her sister has a mutation in the BRCA2 gene.

Family Tree
Hereditary Breast/Ovarian Cancer

= Affected

Hereditary Breast and Ovarian Cancer

Breast cancer 50-85% (9% population risk) Ovarian cancer 10-40% (1.5% population risk)

Men at risk for breast, pancreatic and prostate

Options exist for prevention, early diagnosis and treatment - risks can be reduced for breast and ovarian cancer by up to 90%

Genetic Counseling Appointment

Review features of HBOC Review genetics of HBOC Autosomal dominant inheritance Reduced penetrance Review cancer risks and management options to reduce those risks Discuss option of genetic testing including risks and benefits

Genetic Testing
Pros Decreased anxiety or worry from not knowing Prevent cancer Increased screening Medication Surgery Cons Emotional Impact Increased anxiety or worry if positive test result Insurance and employment issues

Ethical Issues in Genetics

Genetic testing on Children Who owns genetic information? Patient vs. family
Huntingtons Disease

= Affected

When to refer to Genetics

2 or more in family diagnosed with breast cancer <50 3 or more in family diagnosed with breast cancer at any age Ovarian cancer at any age and breast cancer at any age One individual with both breast AND ovarian cancer Man in family with breast cancer Ashkenazi Jewish Heritage, breast/ovarian cancer in fam hx

Questions

Acknowledgements
This presentation was created and donated to the March of Dimes by: Christina Barr, MS, CGC, genetic counselor and former Genetics & Your Practice presenter

Thank you!

For more information contact:

Greater 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/

March of Dimes