Teratogens and Congenital Defects

Question 1

Define congenital abnormality/malformation

Answer 1

Abnormality present at birth

Question 2

What are the 4 broad types of congenital abnormality?

Answer 2

Malformation: misformed (e.g. heart septum)

Deformation: formed then affected (e.g. limb and umbilical bodies)

Dysplasia: expansion of immature cells

Disruption: of a normal process, e.g. cell migration

Question 3

Name some causes of birth defects

Answer 3

Multifactorial inheritance

Chromosomal abnormalities

Mutant genes

Environmental agents, drugs and viruses

Question 4

Define teratogenesis

Define teratogen

Answer 4

The process whereby an abnormality is induced in a developing organism during uterine life caused by a teratogen

Teratogen= foreign agent capable of causing teratogenesis.

Question 5

Give some examples of teratogens and the defects they can cause

Answer 5

Alcohol: fetal alcohol syndrome

Dietary intake: e.g. vitamin A- cleft palate, mandibular hypoplasia, cardiac defects

Medication during pregnancy: e.g. valproate- neural tube defects, facial and limb defects

Viruses: e.g. Rubella - deafness, cataracts, retina dysplasia, microcephaly

Question 6

How can teratogen exposure occur?

Answer 6

Medication used prior to knowledge of pregnancy

Medication necessary for conditions independent of pregnancy (e.g. epilepsy)

Medication used for pregnancy specific conditions (e.g. HTN)

Environmental agents that are impossible to avoid

Question 7

Which dietary teratogens can be avoided/supplemented

Answer 7

Folate deficiency

Zinc: too high or too low

Glucose or ketone bodies: diabetic control

Retinoids: avoid

Question 8

In which period of gestation do the majority of congenital defects occur?

Answer 8

Main embryonic period (2-8 weeks)

Question 9

In which period of gestation do the majority of functional defects and m inor abnormalities occur?

Answer 9

Foetal period

Question 10

How is embryonic damage controlled in the pre-differentiation stage? (1-2 weeks)

Answer 10

All sub-lethal damage repaired

Question 11

In which weeks of gestation is the developing embryo most susceptible to damage? Why?

Answer 11

Weeks 3-8, majority of core systems develop within this phase.

Question 12

What is the highest risk of developmental abnormality in the foetal period?

Answer 12

Functional abnormality

Some (low) risk of structural abnormality

Question 13

At what stage of development are cardiac defects most likely to occur?

Name some possible cardiac defects that can occur here.

Answer 13

Weeks 3-6

• Truncus arteriosis
• Transposition of the great vessels
• Tetralogy of fallot

Question 14

In which weeks of development are upper and lower limb abnormalities most likely to arise?

Name some examples

Answer 14

Weeks 3-5

• Amelia
• Moramelia

Question 15

In which weeks are malformed, low set ears and deafness likely to arise?

Answer 15

Weeks 4-9

Question 16

What influences teratogenicity?

Answer 16

• The ability of the teratogen to access the developing embryo/foetus
• The genome of the embryo/foetus
• Timing and dosage
• Stage of development at exposure to teratogen

Question 17

In which stage of development (weeks) are neural tube defects and mental retardation most likely to occur?

Which is likely to occur earlier in pregnancy and which is more likely to occur later?

Answer 17

Weeks 2-16

Neural tube defects more likely to occur earlier in pregnancy (embryonic period)

Mental retardation most likely to occur later on in pregnancy (later embryonic period and until week 16 (in foetal period))

Question 18

How can a substance be teratogenic?

Answer 18

By causing:

• DNA sequence mutations
• Interruption of DNA or RNA synthesis
• Failure of normal cell - cell interactions
• Interference with cell differentiation
• Chromosomal abnormalities leading to structural/quantitative DNA changes

Question 19

What are the common effects of fetal alcohol syndrome?

Answer 19

Midline facial abnormalities (maxillary):

• Flattened nose
• Absent philtrum and thin top lip
• Heavy epicanthic folds

Neural problems:

• Developmental and behavioural abnormalities

Short, palpebral fissure

Cardiac defects

Question 20

Name some common congenital limb abnormalities

Answer 20

Amelia (absent limb)

Moramelia (partly formed limb)

Phocomelia (seal limb)

Polydactyly (6 digits)

Syndactyly (fused digits)

Question 21

Name some common congenital cardiac abnormalities

Answer 21

Septal defects: atrial or ventricular

Transposition of great vessels

Tetralogy of fallot

Question 22

Name some common neural tube defects

What are they often associated with?

Answer 22

• Meningocoele
• Anencephaly
• Sensory defects of the eyes and ears

Often associated with folic acid deficiency

Question 23

Name some common congenital facial defects and some associated teratogens

Answer 23

Multiple teratogens: anti-epileptics, corticosteroids, retinoids.

• Cleft palate (mainly female) and lip (mainly male
• Tongue: microglossia or macroglossia

Often result from abnormal neural crest cell migration

Treacher-Collins or Pierre Robin syndrome:

• Autosomal dominant or teratogen induced
• Mandibulofacial maldevelopment (zygoma, mandible, maxilla)
• Downslanting palpebral fissure
• Malformed ears and possible conductive deafness