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Flashcards in Teratology Deck (108):
0

What % of zygotes and pregnancies result in normal, healthy babies?

25% zygotes
<50% pregnancies

1

Top 2 causes of infant mortality (up to age 4)

Birth defects
Preterm/Low birthweight

2

Gestational milestones in order

Implantation
Primitive streak
Early Differentiation
Organogenesis Ends
Usual Parturition

3

When does birth defects start in gestation?

Primitive streak onwards
(6 weeks)

4

Why do you have to know the gestational period of a women before giving pills?

primitive streak (6 weeks) to organogensis end (50 weeks) is birth defects

5

Intercellular Signals

Message sent by inducer
Spatial proximity
received by compentent population
∆ developmental state
Maturational or stability

6

What allows for internal rearrangement in humans?

We have time in gestation, development schedules, populations of cell

7

What is the dynamic nature of embryonic development?

There is a small period of time to go back before going forward

Ability to adjust to changing conditions

8

How much do we not know about the cause of birth defects?

50%

9

developmental plasticity

ability of a single gene to express +1 phenotype based on environmental conditions
(BMI >27; T2D, CHD)
Reason to advocate early prenatal care

10

What causes chromosomal abnormaities typically?

nondisjunction during gametogenesis

11

How much ova are aneuploid in humans mostly?

15%, increases in maternal age

12

How else can aneuploid happen?

nondisjunction during cleavage: results in mosaicism of zygote

13

Signs of Trisomy 21/Down Syndrome

Brachycephaly
flat nasal bridge
upward slanding palpebral fissures
Simian crease

14

Fatality in Trisomy 21/Down Syndrome

75% spontaneous abort
20% still born
Survivors survive into 50's

15

Trisomy 18/Edward Syndrome Signs

Flexed digits
Micrognathia
Low set, malformed ears
prominent occiput

16

Fatality in Trisomy 18/Edward Syndrome

50% spontaneously abort
survival rarely past 6 month

17

Signs of Patau Syndrome/Trisomy 13

Cleft lip/palate
Sloping forhead
CNS malformations
Polydactyly

18

Fatality of Patae Syndrome/Trisomy 13

50% spontaneously abort
Rarely survive beyond 6 months

19

Signs of Turner syndrome/45, X

Lymphedema
Lack of secondary sex characteristics
Webbed neck
broad chest

20

Fatality of Turner Syndrome/45, X

1% embryos survive

21

X missing in Turner's syndrome

Paternal X usually

22

47, XXX

Normal female appearance
fertile
20% mentally retarded

23

47, XXY/Klinefelter Syndrome

Male
small testes
aspermatogenesis
long legs
intelligence deficit
gynecomastia

24

47, XYY

Normal male appearance
tall

25

Triploidy 3N

Intrauterine growth retardation
Small trunk
large head

26

What typically causes triploidy 3N

dispermy

27

Fatality of triploidy 3N

live births are extremely rare

28

Tetraploidy 4N

Abort very early
probs due to failure of cytoplasmic cleavage or chromosomal segration at first mitotic cleavage division

29

Nonhomologous DNA translocation caused by

radiation, drugs, chemicals, viruses

30

balanced vs unbalanced translocation

balanced: non DNA lost or added - less severe
unbalanced - more severe

31

Cri du chat syndrome

deletion of short arm of chromosome 5

32

Cri du chat syndrome or deletion of short arm of chromosome 5 results in

microcephaly
severe mental retardation
heart anomalies

33

Duplications can exist as (3)

1. Tandem repeat within chromosome
2. attached to a chromosome
3. As a separate fragment

34

Duplications compared to deletions

More common
Less harmful

35

Inversions

Segment of chromosome is reversed

36

2 types of chromosomal inversion

ParAcentric: single arm
Pericentric: both arms, including the centromere

37

What happens in inversion

interes with homolgous recombination and segration during meiosis

38

Isochromosomes

centromere divides dransversely intead of longitudinally

39

Most common structural defect of X chromosome

Isochromosomes

40

When can mutations not be deliterious?

When good (evolution)
When silent: no effect on protein function or impair function of a redundant gene

41

What disease has a problem with sonic hedgehog?

Holoprosenscephaly

42

What happens in holoprosencephaly?

Failure of forebrain to completely separate into 2 lobes
leads to a wide range of brain, skull and facial defects
(form cleft lip to cyclopia/hypertolorism with proboscis)

43

Dwarfism disease name

Achondroplasia: FGFR3

44

Predisposition for suceptibility or resistance in embryo genotype oftem due to

plymorphisms in drug netabolizing enzymes
(phenytoin/dilantin)

45

Fetal hydantion (dilantin) syndrome

Phenytoin stuck in toxic epoxide intermediate without epoxide hydrolase

46

Fetal hydantion (dilantin) syndrome signs

5% of fetuses
IUGR
microcephaly
mental retardation
altered facies
underdeveloped nails

47

∆s in women during pregnancy

50% increase in plasma volume
"" CO
"" GFR
↓ systemic vacular resistance
" plasma protein binding
Altered salts and mineral metabolism
Greater pulmonary ventilation

48

Toxicities to embryo (3) from mother toxicity

- aminopterin
- methyllmercury
- polychlorinated biphenyls (eh)

49

Toxicity to embryo in stress (3)

steroidal hormones
ethanol
cigarette smoking

50

Toxicity to embryo without significant maternal effects (4)

1. Thalidomide
2. Accutane
3. Diethylstilbestrol
4. Ionizing radiation

51

Preeclampsia

blood vessels in uterus constrict
Restricts blood supply to placneta and increases bp in mother
associated with ↓ VEGF in maternal blood

52

What decreases incidence of preeclampsia

periconecptual multivitamins

53

Risk of birth defects in poor glucose control vs normally

10% to 3%

54

Maternal diabetes associated with (3)

1. Macrosomia (large baby)
2. Spina bifida
3. Heart, Skeletal, Urinary, reproductive, and digestive tract defects

55

Hyperthermia in mother happens in situations of (3)

Fever,
extremely vigorous exercise,
hot tub/sauna

56

What and when: hyperthermia

3-4 weeks gestation when the neural tube is closeing
increased risk of neural tube defects
(including spina bifida to anencephaly)

57

Phenylketonuria (PKU)

defect in phenylalanine metabolism (phylalanine hydroxylase)

58

PKU controlled by

avoiding certain foods high in phenylalinine (meat, fish, eggs, dairy products, nuts, lentis, aspartame)

59

Excess Phe

abnormal brain development and mental retardation
heart defects
behavior problems

60

Difference between malformation and deformation?

Deformation is late in gestation and caused by physical changes

61

Septate Uterus can cause:

-club foot
-hip dislocation
-skull deformation
-reduction defects of limbs, face

62

Oligohydramnios

Low level of amniotic fluid often due to renal agenesis or amnion lea

63

Prader Willi Syndrome

Paternal exposure of hydrocarbon
15q deletion

64

Prader Willi Syndrome results in

hypothalamic dysfunction
hyperphagia
obesity
etc

65

What can somewhat protect the fetus?

Maternal IgG but not well, infections mild or asymptomatic in mother may seriously damage the fetus

66

Rubella Virus/German Measles trad of clinical signs

1. Cataract
Hearing defect
Patent ductus arteriosis

67

Rubella VIRUS/German Measles sensitivity period

Earlier = greater risk
up to 5 weeks of gestation

68

Most common VIRAL infection at birth in US

Cytomegalovirus

69

1/2 of infected infants with cytomegalovirus get: (4)

1. Hearing loss
2. Mental disability
3. Impaired liver function
4. Poor growth

70

Do cytomegalovirus infants get problems at birth?

10% are asymptomatic at birth and manifest problems within first few years of life

71

What type of infection is toxoplasma gondii

Protozoan

72

How is the protozoan infection of toxoplasma gondii spread?

via raw meat and cat feses
(early exposure = greater risk)

73

Symptoms of toxoplasma gondii (10% at birth): (3)

1. Eye infections
2. enlarged liver and spleen
3. jaundice

74

Symptoms of toxoplamsa gondii if later due to reactivation of latent infection

1. Eye infections
2. vision impairment (retinochoroiditis)
3. hearing loss
4. learning disabilities

75

What type of infection is Treponema pallidum (syphilis)

Spirochete bacteria

76

When/How can treponema pallidum (syphilis) be treated?

antibiotic treatment of maternal syphilis before 16 weeks gestation

77

Effects of treponema pallidum?

1. Stillbirth/neonatal death
2. Dental anomalies
3. Deafness
4. Mental retardation
5. Skin, bone lesions
6. Meningitis

78

Do birth defects have pathognomonics?

NO those are unique to a single cause/etiology
birth defect anamolies ARE NOT

79

What things can cause spina bifida as a characteristic not a pathognomonics

1. genetic mutation
2. methotrexate
3. valproic acid
4. maternal diabetes
5. hyperthermia
6. Folate Deficiency

80

Methylmercury in shellfish yielded

itai-itai, convulsions, psychosis, coma, death
in utero: neurological and behavioral disturbances
instability of neck, convulsions, mental retardation, microcephaly, brain damage

81

How does methylmercury cause harm?

Stabilizes microtubules, interferes with neuronal cells proliferation and migration

82

PCBs (polychlorinated biphenyls)

Used in insulators, hydraulic fluids, plastic pains until '77
continued input into environment via disposal of PCB containing products

83

PCDFs (polychlorinated dibenzofurans) - CAUSE OF DEFECTS

byproducts of incineration, smelting, steel production, burning fossil fuels, manufacture of chlorinated compounds, bleaching of pulp and paper

84

PCDDs (polychorinated dibenzo-p-dioxin)

same as PCDF
TCDD = most infamous of all HAH congener = was in defoliant Agent Orange

85

PCDFS (POLYCHLORINATED DIBENSOFURANS) effects

Prematurity, low birth weight, neonatal death
Growth abnormalities
Neurological damage
Hyperpigmentation
Chloracne
Gum and dental disorders
Rock bottom heel
Sperm defects

86

Fetal alcohol syndrome (FAS)

A set of physical and mental birth defects stemming from in utero alcohol exposure

87

Fetal alcohol spectrum disorders (FASD)

Umbrella term describing range of fetal alcohol effects
NOT a clinical diagnosis

88

What is the leading PREVENTABLE cause of mental retardation and birth defects?

FASD
(1 in 100)
(1 in 1000 FAS)
Societal cost: 5.4 billion annually

89

FAS characteristics

Mental Retardation
Small head circumference
Facial abnormalities:
reduced, indistinct philtrum, thin upper lip, epicanthal folds short palpebral fissures, maxillary hypoplasia, poor frontonasal process development
Growth deficits
Microcephaly
Heart liver, kidney defects
Vision and hearing problems

90

FAS features from later exposure

Motor function
hyperactivity
memory, attention, and judgement problems
language problems
difficulties in school

91

Most sensitive period for FAS

1st month of gestation (risky b/c many don't know they're pregnant until the 2nd month)
But functional deficits can result from THRU OUT gestation

92

FAS characteristics mechanism of action

Excessive cell death (especially neurons)
Decreased cell proliferation
Altered cell migration (especially neural crest)
Loss of cell adhesion
Altered neuronal/glial interactions
Altered differentiation

93

Thalidomide

caused teratogenicity if taken when pregnant
Still used for treating leprosy, cancer, certain types blindness

94

Thalidomide effects

Quadruple amelia
Phocomelia

95

Retinoids

Similar to Vitamin A
teratogenic
dangerous b/c fine for girls but 1/2 of pregnancies are unplanned

96

Retinoid Development Toxicity

Craniofacial defects
Heart malformations
Thymic defects
Cleft palate
Eye and ear deformities
CNS defects

97

Sensitivity period for retinoids

3-5 weeks gestation
critical period for cranial neural cret specification

98

Effects of retinoids from

Disruption of HOX gene expression and subsequent effects on cranial and cardiac neural crest cells (and somite-derived structures)

99

Amniocentesis

Invasive Prenatal Screening
Performed at 13 weeks gestation
Fetal cells isolated from small volume of amniotic fluid
Genetic/karyotypic analysis
Risk of miscarriage 1:300

100

Chorionic villus sampling

Invasive prenatal screening
Performed at 8-10 weeks gestation
Chorionic villus cells collected
Genetic/karytypic analysis
Risk of miscarriage 1:100

101

Ultrasound

Non-invasive so used more than the invasive ones
Nuchal translucency ultrasound
Performed at 9-13 weeks gestation
Increased thickness of nuchal fold >3mm
indicates lymphedema and correlates with trisomy 13, 18, 21

Possible risk of neural architecture disturbance so don't use too much

102

Maternal serum analysis

Non-Invasive Prenatal Screening
at 15 weeks
AFP, Estriol, ß-hCG
maternal blood has 6 fetal cells/mL
mostly trophoblasts
Fetal cells differ from maternal cells by surface receptors and methylation patters
cloned, genetic karyotypic analysis performed
no risk of miscarriage

103

High AFP in mother serum =

neural tube defects
other combinations = various trisomies

104

Conditions associated with smoking

spontaneous abortion, preterm delivery, delivery problems, Intrauterine Growth Retardation (IUGR)/Low birth weight
Altered infant bp

105

Anamolies with smoking

Extra digits among children of african descent
Webbing between digits among caucasion males
Not sure about these though

106

Stopping smoking most likely helps decrease infant mortality by

decreasing premature births (17%, 4.5K)

107

Should women gain weight in pregnancy?

Yes, if stop smoking +5-7, its healthy