GENETIC CONDITIONS AND BIRTH DEFECTS
Camila Vieira Shanahan, MS, CGC
Genetic Counselor
Fullerton Genetics Center
February 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.
2.
3.
4.
Cigarettes
Crack/Cocaine
Heroin
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. niaaa.nih.gov/
Source: www.come-over.to/FASCRC/
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 Program
Fullerton 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 Bifida
Three types:
 Spina Bifida Occulta


Meningocele


Vertebrae are slightly
malformed
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 = 23
Egg = 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




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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

Incidence 1:2500

Major features:
Short stature
 Lack of sexual
development at puberty
 Infertility
 Heart defects
 Webbed neck

45, XO
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
Gives additional
1.7-2.8%
risk over general
population
= 6%
http://depts.washington.edu/mednews/vol6/no15/cousins.html
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
Dislocated lenses
Wrist sign
Hand sign
Heart
Arm span
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
Achondroplasia
Diastrophic Dysplasia
Matt
D
Amy
D
A
Jacob
A
Jeremy
Zach
Molly
D
A
D
A
D
A
D
A
Famous People with Dwarfism

Jason Acuna


Arturo Gil - Actor


Skateboarder, Actor
(Jackass Movies/TV)
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 eyelid
Source:www.whick.com
Treacher-Collins

Autosomal dominant

60% new mutation
Preoperative
Postoperative
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?