Genetics: Exam 6

Front 1

what are the Four general principles of teratology?

Back 1

1. Exposure to the teratogen must occur during the critical period, usually, but not always, the first 12 weeks of gestation.
2. Each teratogenic agent produces a specific pattern of anomalies.

3. Teratogens are species specific.

4. Some element of genetic predisposition is likely, since almost no teratogen affects all exposed fetuses.

Front 2

when does Alcohol and ACE inhibitors act.

Back 2

after the first 12 weeks of gestation

Front 3

Does Bendectin cause the same tetratogenic effect on children?

Back 3

NO, wide variey to defects

Front 4

Do twins respond the same to the a common tetrogenic exposure?

Back 4

DZ twins can respond differently to same teratogenic exposure

Front 5

what are the challenges to a tetrogenic studies?

Back 5

1. Background risk exists for congenital anomalies in unexposed controls
2. Ascertainment bias if cases are collected after outcome is known
3. Randomized prospective trials may be unethical if a teratogenic effect is suspected
4. Many confounding variables cannot be controlled: time of exposure, other drugs
5. Genetic susceptibility may vary with racial or ethnic background.
6. Mothers of affected children may have a recall bias compared to control mothers

Front 6

Maternal insulin dependent diabetes leads to what defects

Back 6

Cardiac defects, spina bifida, sacral agenesis, holoprosencephaly, heterotaxy, large birth weight

Front 7

Maternal Phenylketonuria (PKU) leads to what defects

Back 7

Mental retardation, microcephaly and cardiac lesions common in untreated maternal PKU. Low phenylalanine diet should be initiated prior to conception to maintain maternal blood phenylalanine between 2-6 mg/dl.

Front 8

Fetal Alcohol Syndrome leads to what defects

Back 8

Twenty percent of those with IQs in the 50-80 range and 1/6th of those with cerebral palsy are victims of fetal alcohol exposure. However, less than 50% of the offspring of chronically alcoholic women are affected. Children have low birth weight, microcephaly, short palpebral fissures, smooth philtrum, thin upper lip, small nails, behavior and intellectual problems.

Front 9

Folic Acid Responsive Defects leads to what defects

Back 9

Spontaneous abortions (SAb), spina bifida, cleft lip and possibly heart and limb defects are more frequent when folic acid is low in the first trimester.

Front 10

is Folic Acid Responsive Defects a tetrogen

Back 10

no, its a morphogen

Front 11

what does the CDC recommend for the intake of folic acid

Back 11

all women of childbearing age take 400 micrograms/day of folic acid. Mothers of children with spina bifida should take 4mg/day to prevent a recurrence. Folic acid supplementation should begin at least one month before conception to reduce neural tube defects by the maximum 60-70%.

Front 12

Anticonvulsants: Hydantoin and Valproate cause what defect?

Back 12

About 40% of exposed infants have some effects: developmental delay, nail hypoplasia, cleft lip, and dysmorphism. Valproate and carbamazapine increase the chance of spina bifida to 1-2% (background risk 1/1000). Valproic acid is associated with radial ray (thumb or radius) defects

Front 13

What effect does Rubella have?

Back 13

Eighty percent of first trimester infections produce fetal effects: cataracts, intrauterine growth retardation, microcephaly, retinitis, deafness, cardiac defects, mental retardation. More common now in immigrant, unimmunized populations.

Front 14

What effects does Accutane (Isotretinoin) have on fetal development?

Back 14

Risk of SAb is 40%, anomalies 25%. Critical period is 2-5 weeks after conception. CNS, facial palsy, major ear anomalies, conotruncal heart defects, thymic aplasia.

Front 15

Lithium criticle period?

Back 15

Critical period is approximately 4-6 weeks

Front 16

what effect does lithuim have on fetal development?

Back 16

Increased chance of tricuspid atresia (Epstein’s anomaly). Later prospective studies showed weaker effect.

Front 17

what is the critical period of warafin

Back 17

Critical period is first 100 days.

Front 18

what is the effect of warafin?

Back 18

Anomalies in 17-30%: Mental retardation, microcephaly, stippled epiphyses, and optic atrophy. Severe nasal hypoplasia. Phenocopy of chondrodysplasia punctata, a single gene disorder.

Front 19

what is the critical period of Angiotensin converting enzyme inhibitors?

Back 19

Critical period is after the first trimester

Front 20

what is the effect of Angiotensin converting enzyme inhibitors on fetal development?

Back 20

Interferes with renal blood flow causing anuria, oligohydramnios, death in utero due to renal failure

Front 21

what is Thalidomide used for ?

Back 21

Effective therapy for oral ulcers in AIDS, leprosy, chronic graft v. host disease, rheumatoid arthritis, ulcerative colitis

Front 22

what is the mechanism of Thalidomide

Back 22

Mechanism of action is angiogenesis inhibition

Front 23

what are the defects associated with thalidomide?

Back 23

Phocomelia (“seal limb”), polydactyly, cleft lip and palate and other defects in majority of fetuses when given in first trimester.

Front 24

what are the safety precautions for Thalidomide

Back 24

. Two forms of contraception and a negative pregnancy test each month are required before a 28-day refill is given.