Genetic Conditions and Birth Defects

GENETIC CONDITIONS AND BIRTH DEFECTS

Camila Vieira Shanahan, MS, CGCGenetic CounselorFullerton Genetics CenterFebruary 17, 2012

Outline Prenatal Exposures Types of Genetic Conditions

Multifactorial disorders Chromosomal disorders Single gene disorders Mitochondrial disorders

Genetics Clinic

What are birth defects? Birth defects are defined as

abnormalities of structure, function, or body metabolism that are present at birth.

These abnormalities lead to mental or physical disabilities or are fatal.

There are more than 4,000 different known birth defects ranging from minor to serious.

With every pregnancy, the chance for a baby to be born with a birth defect is…

3-5%

Pregnancy Timeline

MAINTAINING A HEALTHY LIFESTYLE IS IMPORTANT DURING PREGNANCY

Which of the following can cause more harm to a fetus?

1. Cigarettes2. Crack/Cocaine3. Heroin4. Alcohol

“Alcohol causes more damage to the developing fetus than any other substance, including marijuana, heroin, and cocaine.”

Institute of Medicine, 1996

Effects of Alcohol Consumption of

alcohol during pregnancy can have devastating effects on the baby

No amount of alcohol is okay

Fetal Alcohol Syndrome The name commonly given to the group of

physical features found in children exposed to alcohol during pregnancy

Common features include: Classic facial features Growth problems in both weight and height Heart, liver, and kidney problems Vision and hearing problems Difficulties with learning, attention, memory,

and problem solving

Characteristic FAS Facial Features

Source: www.come-over.to/FASCRC/

Source: www. niaaa.nih.gov/

Fetal Alcohol Syndrome Approximately 1 in

every 100 children born have some effects of alcohol

The leading known preventable cause of mental retardation and birth defects

It is preventable by avoiding alcohol during pregnancy

Fetal Alcohol Syndrome One child with FAS

costs about $800,000 in health care costs over their lifetime

It is found in all racial and economic groups

The effects are not reversible and do not go away with time

Effects of Smoking Smoking during

pregnancy can also affect the baby

Babies born to women who smoke are usually small at birth (under 5 ½ pounds)

Preterm delivery is also common

Possible low IQ

Effects of Medications Medications you

take can also be harmful during pregnancy

The most devastating ones include Accutane and anti-seizure medications

Ask your doctor about medications you are taking

Pregnancy Exposure ProgramFullerton Genetics Center

Effects of Good Prenatal Care

Good prenatal care is the first step to ensuring a healthy baby

This includes eating healthy, exercising, getting enough sleep, and seeing your doctor

However, there is never any guarantee

Types of genetic diseases

Multifactorial disorders Chromosomal disorders Single gene disorders Mitochondrial disorders

Multifactorial Disorders No clear inheritance pattern

Recurrence risk difficult to estimate

Combination of genetic and environmental factors

The Neural Tube

Neural Tube Defects If the neural tube doesn’t zipper on the

back, the baby will have spina bifida

If the tube is open at the head, the baby will have anencephaly

Spina Bifida Occurs in 1 out of every 1,000 births One of the most common birth defects Cost to society is about $532,000 for

each child with spina bifida Surgery is done immediately following

birth to close the opening Some surgery is also being done while

the baby is still in the womb

Spina Bifida

Spina BifidaThree types: Spina Bifida Occulta

Vertebrae are slightly malformed

Meningocele Opening in the

vertebrae; membranes and fluid protrude

Myelomeningocele Opening in the

vertebrae; membranes, fluid, and spinal cord protrude

Spina Bifida

Spina Bifida- Who’s at Increased Risk? Women who have previously had a child

with a NTD Women who are insulin-dependent

diabetics Women using some anti-seizure

medications Women with medically diagnosed obesity Women exposed to high temperatures

early in pregnancy It is more common in Caucasian and

Hispanic women

Spina Bifida- How do you prevent it?

Folic acid!! The recommended daily allowance is 400

micrograms But it can be as much as 4000 micrograms

in women at high-risk Folic acid should be taken before

conception through the third month of pregnancy

May reduce your risk by 70% Half of all pregnancies are unplanned

All women of child bearing age should take a vitamin with folic acid!

Anencephaly Occurs when the neural tube doesn’t

close at the back of the skull Without the complete skull, the brain

fails to develop These children are born with a brain

stem, but no brain Most survive only hours or days after

birth

Anencephaly

Anencephaly

Cleft Lip and Palate Occurs in 1 in every 700 births The lip and palate form sometime around 6-12

weeks of pregnancy Surgery is done to close the lip and palate

Children usually do very well with the surgery and develop normal speech

Some studies have shown that folic acid can also be useful in preventing cleft lip and palate

More common in children of Asian descent Has many causes, some of which are genetic

and not preventable

Cleft Lip and Palate

Cleft Lip and Palate

Unilateral Bilateral

Cleft Lip: Before & After

Other multifactorial disorders Asthma

Diabetes

Cardiovascular disease

Cancer

Effects of Genetics Genes also play a role

in how we develop Some birth defects are

due to changes in our genes

These cannot be predicted or prevented

Examples: Down syndrome Some heart defects Sickle cell disease Cystic fibrosis

What is a genetic condition? Any condition caused by a change in a

gene that leads to physical and/or mental differences

May present at birth or later in life

These gene-changes can happen by chance or can be inherited

Background on genetics

Every human being has about 30,000 genes that determine everything from eye color to the development of our physical and biochemical systems.

Genes come in pairs, and we inherit half of our genes from each parent.

Genes are packaged on 46 chromosomes inside our cells

Sperm = 23Egg = 23

Fertilized egg = 46

Typical male 46 XY

Typical female 46 XX

Collecting cells for chromosome analysis

Blood

Tissue

Chorionic villi sampling (CVS)

Amniocentesis

Types of genetic diseases

Multifactorial disorders Chromosomal disorders Single gene disorders Mitochondrial disorders

Chromosome disorders Extra chromosome

Missing chromosome

Rearranged chromosomes

Extra or missing piece of chromosome

Down syndrome 47, +21

Down syndrome Facial features similar to one another Mental retardation Heart problems Intestinal problems Vision and hearing

problems Number of other birth

defects and health problems

Turner syndrome 45, XO

Turner syndrome 45, XO Incidence 1:2500

Major features: Short stature Lack of sexual

development at puberty

Infertility Heart defects Webbed neck

Single Gene Disorders Disorders in which single genes are altered.

Sometimes the altered genes occur pre/post-fertilization, or can be inherited from a parent in the following pattern:

Autosomal recessive Autosomal dominant X-linked

Autosomal recessive Recessive gene on

an autosome Inherit two non-

working copies to be “affected”

Two “carriers” must each pass on the non-working copy. Chance to have an affected child is 25%.

How much of the world’s population is married to their cousin?A. 1 out of 1,000 (0.1%)

B. 1 out of 100 (1%)

C. 1 out of 10 (10%)

D. 1 out of 3 (33%)

First cousins have an increase risk of having a child with a birth defect

http://depts.washington.edu/mednews/vol6/no15/cousins.html

Gives additional

1.7-2.8% risk over general

population

= 6%

Sickle Cell Anemia Incidence 1 in 500

(African Americans) Carrier frequency is 1 in 8

Mutation in B-globin gene on chromosome 11

Features: Joint, stomach, chest or

muscle pain Swelling of abdomen Infections Damage to organs

Cystic fibrosis Incidence 1 in 2500 (Caucasians)

Carrier frequency 1 in 25

CF gene on chromosome 17

Features: Develop thick mucus Sterility in males Abnormal sweat glands Pancreatic insufficiency Life expectancy 30 years in severe cases

Autosomal dominant

Dominant gene on an autosome

Inherit one non-working copy to be “affected”

Parent with genetic condition has a 50% chance of passing to offspring

Marfan syndrome Incidence 1 in

5,000 Due to changes in

the fibrillin 1 precursor (FBR 1) gene on chromosome 15

Major features: Tall, thin stature Heart defect Pectus excavatum Joint laxity

Marfan syndrome – Physical Exam

Hand sign

Arm span

Dislocated lenses

Wrist sign

Heart problems

Marfan syndrome

Famous People with Marfan Syndrome

Flo Hyman – US olympic volleyball player – died of aortic rupture in 1986 at a game in Japan

Abraham Lincoln – suspected diagnosis

Vincent Schiavelli – actor from Ghost,

People vs. Larry Flynt, Tomorrow Never Dies, etc.

Honorary Co-Chair of National Marfan Society

Died in 12/2005 of lung cancer

Neurofibromatosis Incidence 1 in 3000

Mutations in NF1 (17q) and NF2 (22)

Common features: Café au lait patches Neurofibromas Freckling in

groin/armpits

Achondroplasia

Incidence: 1 in 25,000

Mutation in fibroblast growth receptor 3 (FGFR 3) on chromosome 4

Major features: Short limbs Curvature of lower

spine Prominent forehead

Little People, Big World

Little People, Big World

Matt

D A D A

D A D A D A D A

Amy

ZachMolly

JeremyJacob

Diastrophic Dysplasia

Achondroplasia

Famous People with Dwarfism

Jason Acuna Skateboarder, Actor

(Jackass Movies/TV)

Arturo Gil - Actor Charmed, Ally

McBeal, Just Shoot Me, The Man Show

Zach Roloff Little People, Big

World, TLC

Other Autosomal Dominant Conditions

Ehlers Danlos Connective Tissue

Disorder Stretchy Skin Loose Joints – Flexible Risk for Severe Joint

Pain

Osteogenesis Imperfecta (OI) 1 in 10,000 live

births

Most cases of OI are AD and are new mutations

definition: “osteo” = bones “genesis” = creation

of “imperfecta” =

imperfect

Osteogenesis Imperfecta (OI) Mutation in gene that

affects type 1 collagen

There are six types of OI type II is most serious

OI

Treacher-Collins Features include:

malar hypoplasia with downslanting PFs

malformation of external ear

conductive deafness cleft palate small face defect of lower

eyelidSource:www.whick.com

Treacher-Collins Autosomal dominant

60% new mutation

PostoperativePreoperative

Source:www.craniofacialcenter.com

X-linked Recessive Usually affects only

males

Carrier females have a 50% chance of passing on altered X

Duchenne Muscular Dystrophy

Incidence 1 in 3500 males

DMD gene on X chromosome

Features: Progressive muscle

weakness Loss of muscle Death by age 25 years

(cardiac failure)

Mitochondrial Disorders

The mitochondria are organelles outside of the nucleus that are the cell’s batteries

They have their own genetic material

They are inherited only from the mother

Roles of genetic professionals

Clinical geneticist

Genetic counselor

Laboratory geneticist

Important Components of a Genetics Visit

Family History (Pedigree) Age or date of birth (and, for all family members who have passed on,

age at death and cause of death). Medical problems such as:

Cancer Heart disease Diabetes Asthma Mental illness High blood pressure Stroke Kidney disease Alcoholism Birth defects such as spina bifida, cleft lip, heart defects, others. Learning problems, mental retardation. Vision loss/hearing loss at a young age (remember to record the

age it began). Family members with other known medical problems

Medical History

• May be provided through referring physician, collection of medical records, or interviews with the patient or family members

• Often provides important clues pointing to a particular diagnosis

• Identifies the family’s main areas of concerns and specific questions that need to be addressed during the session

• Another important opportunity to complete a psychosocial assessment

Physical Examination

• Helps to establish or rule out a diagnosis

• Based on a standard physical examination

• Incorporates additional elements:

• Dysmorphology examination

• Specific elements may be included dependent upon diagnoses under consideration

Morphology

• (n) The branch of biology that deals with the structure of animals• Basically the study of our pieces & parts and how they fit together

Dysmorphology Altered development The study of malformation syndromes

What does Dysmorphology have to do with Genetics?

Clinical Geneticists use dysmorphology to give them clues as to what genetic syndrome (if any) an individual has

A genetic syndrome is often like a puzzle and the dysmorphic features are like the puzzle pieces

QUESTIONS?