32. Congenital Malformations and Their Causes: Human Malformations

  1. Human malformations occur in 2-3% of births. Some examples of these are
      1. Phocomelia: limb anomaly spontaneously create Seen in 1/100,000 births
        1. A typical lesion of thalidomide: 10% of the women who took the drug during the critical period had babies with this anomaly
      2. Coelosomy: a defect of closure of the abdominal wall whereby the normally developed abdominal viscera are found in an extra-abdominal position
      3. Craniorrhachischisis: complete failure of the neural tube to close
        1. There are angiomatous degeneration of nervous tissue, absence of the cranial vault, and absence of the posterior arches of the vertebra
    2. DOUBLE MONSTERS OR DOUBLE-TYPE MALFORMATIONS can be considered as nonseparated twins with the degree and type of fusion being variable
      1. Janus-type (janiceps) cephalothoracopagus (pagus, meaning something fastened)
      2. Asymmetric thoracopagus
      3. Acardia is one of a pair of monozygotic twins which has degenerated after a failure of vascularization. Structures already present regress, ending in the formation of what looks like an amorphous mass with no organization
    3. EXPERIMENTAL MALFORMATIONS: the mammalian embryo, despite its apparent protection, is very sensitive to the influence of various external teratogenic agents. Most of the malformations, seen in humans clinically, have been reproduced experimentally
      1. Classification of teratogenic factors: usually described in 5 major groups
      2. Physical factors: x-rays, radiation, et
      3. Chemical factors: hypoglycemia, antitumor drugs, neurepileptics, et
      4. Nutritional factors: hyper- or hypovitaminosis, mineral excess, or deficiencies, vitamin imbalance, et
      5. Hormonal factors: use of androgens, synthetic progesterones, cortisone, et
      6. Infectious factors: toxoplasmosis, rickettsioses, Asian flue, and viruses
      7. Viruses: especially rubella or German measles, cytomegalovirus, herpes simplex virus, measles, mumps, hepatits, poliomyelitis, chickenpox, syphilis, ECHO virus, and Coxsackie virus. A number have been implicated but not all cause malformations
      8. Mode of action of teratogenic factors: the effect depends predominantly on the stage of intervention of the agent (chronologic factor) and the genetic constitution (constitutional factor). Several types of sensitivity are listed

        Time or stage of sensitivity

        Before implantation: external agents, according to their intensity, provoke either completely rreversible lesions or definitive mortal lesions

        After implantation and during the entire period of active morphogenesis: this is the principle teratogenic period because a primordium is most sensitive to teratogenic actions at the time of its appearance

        a) The same substance can produce different malformations if given at different stages of morphogenesis

        b) When more than 1 primordium develop simultaneously, the same agent can result in multiple malformations

        Species sensitivity: an agent teratogenic for 1 species may not be so for another

        Strain sensitivity: even in the same species, the percentage of malformations seen with any substance can vary according to strain and even the line

        Individual sensitivity: even in the same animal litter subjected to a teratogenic influence, certain individuals react differently and may be free of any malformations. Even those malformed are not so to the same degree necessarily. Different metabolic peculiarities may explain these individual variations and also those seen between strains

congenital malformations and  their causes: human malformations: image #1