Concepts in Congenital Anomalies

Question 1

Give the name and an example of the following definitions:
1. Primary errors of morphogenesis in which there is an intrinsically abnormal developmental process
2. Result from secondary destruction of an organ or body region that was previously normal in development
3. Represent an extrinsic disturbance in development with localised or generalised compression of the growing foetus
4. A cascade of anomalies triggered by one initiating aberration
5. A constellation of congenital abnormalities believed to be pathologically related that cannot be explained on the basis of a single, localised, initiating defect

Answer 1

1. Malformations e.g. polydactyly
2. Disruptions e.g. amniotic bands
3. Deformations e.g. club feet
4. Sequence e.g. oligohydramnios (or Potter) sequence
5. Malformation Syndrome e.g. Down syndrome

Question 2

As well as genetic origin, congenital anomalies can be caused by environmental exposures, or be multifactorial. List the four types of environmental causes, and give and example of each:

Answer 2

• Maternal/placental infections e.g. Rubella
• Maternal disease states e.g. diabetes
• Drugs and chemicals e.g. alcohol
• Irradiation

Question 3

The intrauterine development of humans can be divided into two phases, 1) the early embryonic period (up to 9 weeks) and 2) the foetal period (terminating at birth). At what point in time is the pregnancy extremely susceptible to teratogenesis?

Answer 3

Between the third and ninth weeks, particularly the fourth and fifth. (This is the time when organs are being crafted from the germ cell layers).

Question 4

What two general principles of developmental pathology are relevant regardless of the etiologic agent?

Answer 4

• The timing of the prenatal teratogenic insult has an important impact on the occurrence and type of anomaly produced.
• The interplay between environmental teratogens and intrinsic genetic defects is exemplified by the fact that features of dysmorphogenesis caused by environmental insults can often be recapitulated by the genetic defects in pathways targeted by these teratogens.