Teratology Flashcards
0
Q
Top 2 causes of infant mortality (up to age 4)
A
Birth defects
Preterm/Low birthweight
1
Q
What % of zygotes and pregnancies result in normal, healthy babies?
A
25% zygotes
<50% pregnancies
2
Q
Gestational milestones in order
A
Implantation Primitive streak Early Differentiation Organogenesis Ends Usual Parturition
3
Q
When does birth defects start in gestation?
A
Primitive streak onwards
6 weeks
4
Q
Why do you have to know the gestational period of a women before giving pills?
A
primitive streak (6 weeks) to organogensis end (50 weeks) is birth defects
5
Q
Intercellular Signals
A
Message sent by inducer Spatial proximity received by compentent population ∆ developmental state Maturational or stability
6
Q
What allows for internal rearrangement in humans?
A
We have time in gestation, development schedules, populations of cell
7
Q
What is the dynamic nature of embryonic development?
A
There is a small period of time to go back before going forward
Ability to adjust to changing conditions
8
Q
How much do we not know about the cause of birth defects?
A
50%
9
Q
developmental plasticity
A
ability of a single gene to express +1 phenotype based on environmental conditions
(BMI >27; T2D, CHD)
Reason to advocate early prenatal care
10
Q
What causes chromosomal abnormaities typically?
A
nondisjunction during gametogenesis
11
Q
How much ova are aneuploid in humans mostly?
A
15%, increases in maternal age
12
Q
How else can aneuploid happen?
A
nondisjunction during cleavage: results in mosaicism of zygote
13
Q
Signs of Trisomy 21/Down Syndrome
A
Brachycephaly
flat nasal bridge
upward slanding palpebral fissures
Simian crease
14
Q
Fatality in Trisomy 21/Down Syndrome
A
75% spontaneous abort
20% still born
Survivors survive into 50’s
15
Q
Trisomy 18/Edward Syndrome Signs
A
Flexed digits
Micrognathia
Low set, malformed ears
prominent occiput
16
Q
Fatality in Trisomy 18/Edward Syndrome
A
50% spontaneously abort
survival rarely past 6 month
17
Q
Signs of Patau Syndrome/Trisomy 13
A
Cleft lip/palate
Sloping forhead
CNS malformations
Polydactyly
18
Q
Fatality of Patae Syndrome/Trisomy 13
A
50% spontaneously abort
Rarely survive beyond 6 months
19
Q
Signs of Turner syndrome/45, X
A
Lymphedema
Lack of secondary sex characteristics
Webbed neck
broad chest
20
Q
Fatality of Turner Syndrome/45, X
A
1% embryos survive
21
Q
X missing in Turner’s syndrome
A
Paternal X usually
22
Q
47, XXX
A
Normal female appearance
fertile
20% mentally retarded
23
Q
47, XXY/Klinefelter Syndrome
A
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
