Congenital abnormalities

Question 1

Define congenital abnormalities

Answer 1

Abnormalities that exist at or before birth

Question 2

Name the 4 types of clinically significant congenital abnormalities

Answer 2

1) Malformation
2) Disruption
3) Deformation
4) Dysplasia

Question 3

What is malformation?

Answer 3

A morphologic defect of an organ, part of an organ, or larger region of the body resulting from an intrinsically abnormal developmental process

Question 4

What is disruption?

Answer 4

A morphologic defect of an organ, part of an organ, or larger region of the body resulting from the extrinsic breakdown of, or an interference with, an originally normal developmental process

Question 5

What is deformation?

Answer 5

An abnormal form, shape, or position of a part of the body caused by mechanical force

Question 6

What is dysplasia?

Answer 6

An abnormal organisation of cells into tissue(s) and its morphologic result(s) - a process and consequence of dyshistogenesis

Question 7

Define teratogenesis

Answer 7

A process whereby an abnormality is induced in a developing organism during uterine life by a foreign agent (teratogen)

Question 8

What abnormalities could an excess of vitamin A cause?

Answer 8

Cleft palate, mandibular hypoplasia, heart defects

Question 9

What could alcohol cause?

Answer 9

Fetal alcohol syndrome

Question 10

What abnormalities could rubella cause?

Answer 10

Deafness, cataracts, retinal dysplasia, microcephaly

Question 11

What abnormalities could cytomegalovirus and toxoplasma gondola cause?

Answer 11

Microcephaly and micropthalmia

Question 12

What abnormalities could X-ray cause?

Answer 12

Microcephaly, spina bifida, cleft palate

Question 13

What abnormalities could valproate cause?

Answer 13

Neural tube defects, facial defects, limbs

Question 14

When is the foetus at greatest risk of damage from a teratogen?

Answer 14

3-16 weeks; the period during which multiple systems are developing

Question 15

Why is the embryo not at risk from teratogens at 0-2 weeks?

Answer 15

It either repairs or dies

Question 16

What happens to the risk of structural abnormality during gestation?

Answer 16

Look at graph on slide 22

Question 17

What happens to the risk of functional abnormality during gestation?

Answer 17

Look at graph on slide 22

Question 18

What can influence the teratogenicity of a substance?

Answer 18

1) Teratogen must contact developing embryo/fetus
2) Timing or period of development at point of exposure
3) Duration and dosage of exposure
4) Fetus susceptibility eg. due to genotype

Question 19

How can a substance be teratogenic?

Answer 19

1) Mutational changes in DNA sequences
2) Interruption of DNA or RNA synthesis
3) Failure of normal cell migrations
4) Failure of normal cell-to-cell interactions
5) Interference with cell differentiation
6) Chromosomal abnormalities leading to structural or quantitative changes in DNA

Question 20

What are Wilson’s six general principles of teratology?

Answer 20

The final manifestations of abnormal development are death, malformation, growth retardation and functional disorder.

Susceptibility of the conceptus to teratogenic agents varies with the developmental stage at the time of exposure.

Teratogenic agents act in specific ways (mechanisms) on developing cells and tissues in initiating abnormal embryogenesis (pathogenesis).

Manifestations of abnormal development increase in degree from the no-effect to the totally lethal level as dosage increases.

The access of adverse environmental influences to developing tissues depends on the nature of the agent.

Susceptibility to a teratogen depends on the genotype of the conceptus and on the manner in which the genotype interacts with environmental factors.

Question 21

Define teratology

Answer 21

Refers to the study of the types, patterns, mechanisms and causes of congenital abnormalities

Question 22

What are the two types of congenital diaphragmatic hernia?

Answer 22

Bochdalek type is most common (posterolateral diaphragm)

Morgagni hernia are less common (anterior part of diaphragm)

Commonly due to diaphragmatic malformation

Question 23

What are some presentations of fetal alcohol syndrome?

Answer 23

Midline facial abnormalities (maxillary)

Absent philtrum

Thin top lip

Thick/pronounced epicanthic folds

Flattened nose

Short palpebral fissure

Heart defects

Neural issues: Behavioural and developmental

Question 24

Describe the 3 different types of congenital limb defects

Answer 24

Amelia = no limb
Phocomelia = "seal limb"
Meromelia = part limb

Question 25

What can be some causes of congenital limb defects?

Answer 25

• Prescribed medication (e.g. thalidomide)
• Dietary (e.g. Retinoids or Vitamin A derivatives)
• Mechanical (e.g. Amniotic bands occlude blood supply)

Question 26

What are the 3 cardiac congenital abnormalities?

Answer 26

1) Tetraology of Fallot
2) Common/persistent truncus
3) Transposition of the great vessels

Question 27

What can increase the risk of cardiac defects?

Answer 27

Associated with teratogens e.g. tobacco smoke

Obesity and pre-existing maternal diabetes may increase risk

Defects (e.g. septal) can be associated with neural crest cell migration issues

Question 28

Name some neural tube defects

Answer 28

Anencephaly, myeloshisis, meningocoele

Question 29

What can increase the risk of neural tube defects?

Answer 29

Associated with dietary deficiency of folic acid (Vitamin B9)

Associated with teratogens such as valproate, X-ray

May be seen more often in mothers with pre-existing health conditions e.g., diabetes, obesity

Question 30

What are some cranial, ocular and auricular defects?

Answer 30

Microcephaly
Anopthalmia
Micropthalmia
Anotia
Microtia

Question 31

What teratogens can cause cleft palate and lip?

Answer 31

Antiseizure drugs, retinoids, corticosteroids, tobacco smoking

May result from abnormal neural crest cell migration

Question 32

How many live births does cleft lip alone affect vs. cleft palate and lip?

Answer 32

Cleft lip alone (1:2800 live births)

Cleft palate and cleft lip (1:1600)

Question 33

What are some presentations of pharyngeal arch one maldevelopment?

Answer 33

Mandibulofacial maldevelopment/dysostosis(zygoma, mandible & maxilla)

Downward slanting palpebral fissure

Malformed ears (pinna)

Possible conductive deafness

Treacher-Collins or Pierre Robin Syndrome
Autosomal dominant condition

Can be teratogen-induced(e.g., alcohol, retinoids, maternal diabetes