Factors participating on the congenital anomalies genesis:
- genetic factors: responsible for approximately 10 – 15% of CAs, are associated with chromosomal aberrations or originate in gene mutations
- environmental factors: so-called teratogens, cause another 10 – 15% of CAs
- multifactorial causes and factors not yet known: (70 – 80% VVV)
Teratogens and genetic factors can interfere with normal morphogenesis of the fetus on several levels. For example: cell migration, proliferation, interaction, apoptosis etc. can all be affected.
The sensitivity of the fetus to damage causing factors changes during its development. The first trimester of gravidity is the time, when the embryo is highly sensitive to teratogens, while in the second and third trimester (with organogenesis practically finished) the sensitivity decreases. This means that the sooner the damage occures, the more serious the consequences are. The co-called critical stage of the fetus is from the 3rd to the 9th week of gestation. Critical stages of the organs are specific for each organ and slightly vary from one another:
- Central nervous system and cardiovascular system: cca 3 – 6th week of gestation.
- Senses — eyes and ears — cca 4 – 9th week of gestation.
- Limbs: from the end of 4th week to the middle of 8th week of gestation.
- Palate and teeth: 6 – 8th week of gestation.
- External genitalia: 7 – 9th week of gestation.
The stage of gravidity is not the only important factor. Intensity of the teratogenic agent is important as well. Strong agents usually cause death of the fetus, therefore malformations are more likely to be caused by less intensive insults. During the first 2 weeks of development, the embryo is not very sensitive to teratogens, so there is either no damage at all, or the whole conceptus dies (which is less frequent).
Hypoplastic femur, Macro, autopsy (72066)