Congenital anomalies. Classification. Exogenous and endogenous teratogens.
Congenital anomalies are structural defects that are present at birth, although some only become apparent later. The etiology of such anomalies is listed below:
- Genetic
- Chromosomal aberrations
- Mendelian inheritance
- Environmental
- Infections
- Maternal diseases
- Drugs and chemicals
- Multifactorial
Mnemonic: the infections that cause congenital anomalies are the TORCH group: Toxoplasma, Other (syphilis, varicella-zoster, parvovirus B19, Zika), Rubella, Cytomegalovirus and Herpes simplex virus. Rubella in the first trimester classically gives cataract, deafness and heart defects.
We generally categorise congenital anomalies as either structural or functional (metabolic).
- Structural
- Polydactyly
- Syndactyly
- Cleft lip (with or without cleft palate)
- Cyclopia
- Microcephaly
- Functional
- Glucose-6-Phosphate dehydrogenase deficiency
- Galactose Kinase deficiency
- Phenylketonuria
Polydactyly: X-ray of a hand with an extra digit, a structural congenital anomaly.
Image: “Polydactyly 01 Lhand AP” by en:User:Drgnu23 , subsequently altered by en:user:Grendelkhan , en:user: Raul654 , and en:user:Solipsist ., CC BY-SA 3.0, via Wikimedia Commons.
Regarding exogenous and endogenous teratogens, a teratogen is a substance which causes malformations in a developing fetus (from the greek tera meaning monster). Exogenous substances include Alcohol, Folic acid antagonists, Androgens, phenytoin, Thalidomide, Warfarin, 13- cis retinoic acid and others. Endogenous factors are hereditary, and pertain to single gene inherited disorders (e.g. PKU), multigenic factors (Diabetes) or chromosomal abnormalities (Trisomy 21, Downs).
Example: thalidomide in early pregnancy causes phocomelia (short or absent limbs); alcohol causes fetal alcohol syndrome (growth retardation, microcephaly, smooth philtrum, heart defects); warfarin causes nasal hypoplasia and stippled epiphyses; 13-cis-retinoic acid (isotretinoin) causes CNS, heart and facial defects. Embryos are most sensitive between weeks 3 and 8.