1. Genetic Conditions and Birth Defects
Camila Vieira Shanahan, MS, CGC
Genetic Counselor
Fullerton Genetics Center
February 17, 2012

2. Outline Prenatal Exposures Types of Genetic Conditions Genetics Clinic
Multifactorial disorders
Chromosomal disorders
Single gene disorders
Mitochondrial disorders
Genetics Clinic

3. 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.

4. With every pregnancy, the chance for a baby to be born with a birth defect is…
3-5%

5. Pregnancy Timeline

6. Maintaining a healthy lifestyle is important during pregnancy
What do you think having a healthy lifestyle might mean?

7. Which of the following can cause more harm to a fetus?
Cigarettes
Crack/Cocaine
Heroin
Alcohol

8. “Alcohol causes more damage to the developing fetus than any other substance, including marijuana, heroin, and cocaine.”
Institute of Medicine, 1996

9. Effects of Alcohol
Consumption of alcohol during pregnancy can have devastating effects on the baby
No amount of alcohol is okay
What kinds of effects do you think alcohol can cause during pregnancy?

10. 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

11. Characteristic FAS Facial Features
Source: www. niaaa.nih.gov/
Source:

12. 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

13. 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

15. Effects of Smoking Smoking during pregnancy can also affect the baby
                                       
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
What effects do you think smoking might have on a baby?

16. 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
Are medications usually something you would think would be harmful to a baby? What could you do to find out?

17. Pregnancy Exposure Program Fullerton Genetics Center
(800)

18. Effects of Good Prenatal Care
                                            
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

19. Types of genetic diseases
Multifactorial disorders
Chromosomal disorders
Single gene disorders
Mitochondrial disorders

20. Multifactorial Disorders
No clear inheritance pattern
Recurrence risk difficult to estimate
Combination of genetic and environmental factors

21. The Neural Tube

22. 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

23. 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

24. Spina Bifida

25. Spina Bifida Three types: Spina Bifida Occulta Meningocele
Vertebrae are slightly malformed
Meningocele
Opening in the vertebrae; membranes and fluid protrude
Myelomeningocele
Opening in the vertebrae; membranes, fluid, and spinal cord protrude

26. Spina Bifida

27. 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

28. 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!
Not all cases of spina bifida are preventable. Some women who take the recommended amount of folic acid still have children with neural tube defects and we believe there is some underlying genetic cause that explains this.

29. 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

30. Anencephaly
The presence of the brain stem allows these children to breathe and their hearts to beat, but they have no cognitive function.

31. Anencephaly

32. 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

34. Cleft Lip and Palate

35. Cleft Lip and Palate
Bilateral
Unilateral

36. Cleft Lip: Before & After

37. Other multifactorial disorders
Asthma
Diabetes
Cardiovascular disease
Cancer

38. 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
Explain some genes and chromosomes, show karyotype

39. 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

40. 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

41. Sperm = 23
Egg = 23
Fertilized egg = 46

43. Typical male 46 XY

44. Typical female 46 XX

45. Collecting cells for chromosome analysis
Blood
Tissue
Chorionic villi sampling (CVS)
Amniocentesis

46. Types of genetic diseases
Multifactorial disorders
Chromosomal disorders
Single gene disorders
Mitochondrial disorders

47. Chromosome disorders Extra chromosome Missing chromosome
Rearranged chromosomes
Extra or missing piece of chromosome

48. Down syndrome , +21

49. 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

50. Turner syndrome 45, XO

51. Turner syndrome 45, XO Incidence 1:2500 Major features: Short stature
Lack of sexual development at puberty
Infertility
Heart defects
Webbed neck

52. 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

53. 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%.

54. 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%)

55. Gives additional 1.7-2.8% risk over general population
First cousins have an increase risk of having a child with a birth defect
Gives additional % risk over general population
= 6%

56. 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

57. 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

58. 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

59. 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

60. Marfan syndrome – Physical Exam
Hand sign
Arm span
Dislocated lenses
Wrist sign
Heart
problems

61. Marfan syndrome

62. Famous People with Marfan Syndrome
Flo Hyman – US olympic volleyball player – died of aortic rupture in 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

63. Neurofibromatosis Incidence 1 in 3000
Mutations in NF1 (17q) and NF2 (22)
Common features:
Café au lait patches
Neurofibromas
Freckling in groin/armpits

64. 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

65. Little People, Big World

66. Little People, Big World
Achondroplasia
Diastrophic Dysplasia
Matt
Amy
D A
D A
Jacob
Jeremy
Zach
Molly
D A
D A
D A
D A

67. 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

68. Other Autosomal Dominant Conditions
Ehlers Danlos
Connective Tissue Disorder
Stretchy Skin
Loose Joints – Flexible
Risk for Severe Joint Pain

69. 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

70. Osteogenesis Imperfecta (OI)
Mutation in gene that affects type 1 collagen
There are six types of OI
type II is most serious

71. OI

72. Treacher-Collins Features include:
malar hypoplasia with downslanting PFs
malformation of external ear
conductive deafness
cleft palate
small face
defect of lower eyelid
Source:

73. Treacher-Collins Autosomal dominant 60% new mutation Preoperative
Postoperative
Source:

74. X-linked Recessive Usually affects only males
Carrier females have a 50% chance of passing on altered X

75. 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)

76. 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

77. Roles of genetic professionals
Clinical geneticist
Genetic counselor
Laboratory geneticist

78. Important Components of a Genetics Visit

79. 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

81. 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

82. 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

83. 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
Discuss the basics of Morphology
Webster's defines “Morphology” as the branch of biology that deals with the structure of animals
Basically it is a study of our pieces and parts and how they fit together

84. Dysmorphology
Altered development
The study of malformation syndromes

85. 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
Clinical Geneticists try to figure out what may be causing a person’s symptoms
They look at the different symptoms and try to see if they fit together to fit into a known Syndrome
So, you can think about a person’s dysmorphic features as puzzle pieces
We try to fit them together and see if we can create a picture of a known syndrome
Why is it good to know what syndrome someone has?
There may be other health problems that we are missing
It may tell us what treatment would work best

86. Questions?