A Practical Approach, Second Edition=Ronald D. Ho.pdf

HUMAN STUDIES 811from monstrous, usually lethal conditions, through severe and handicapping conditions, to conditionsthat can be repaired to more or less complete normality. Even conditions that only havecosmetic significance or that are so insignificant that the individual can live a completely normallife are also sometimes included.We can illustrate this with various results of a disturbance of the closure of the neural folds toform a neural tube, the embryonic process that leads to the formation of the central nervous system.In the most severe instances, an infant with anencephaly is born; remnants of a heavily malformedbrain lie exposed, and the infant is stillborn or dies during the first few days after birth. A disturbanceoccurring at a slightly later time and hitting more caudal parts of the nervous system may lead toa spina bifida aperta, with an open spine and herniation of the spinal cord and meninges. Whensevere, this leads to pareses and hydrocephaly, with severe brain damage and perhaps lifelonghandicap. In less severe forms, neurosurgery can correct the conditions, sometimes with little orno remaining handicap and normal mental development. In still less pronounced instances, a spinabifida occulta may develop, with an opening of the spine but with a normal or near normal spinalcord. In most instances, this gives no problems for the carrier, although it sometimes results indisturbances of bladder innervation.2. Classification and GroupingThe classification of congenital malformations is usually based on the ICD (International Classificationof Diseases) codes, possibly with extensions. It should be realized that the ICD code isconstructed for clinical use and is often not specific enough for detailed studies of congenitalmalformations. Thus, specially designed coding systems that enable a greater specification than ispermitted by the ICD code have sometimes been used.Congenital malformations are a very heterogeneous group of conditions from the point of viewof aetiology and pathogenesis. It is therefore rather useless to analyze this outcome as the totalmalformation rate, and some division into categories must be made. How such a division shouldbe made can be debated. A common method is to use organ system subdivisions, but the group“limb malformations,” for example, contains many very different subgroups. These could includelimb reductions, polydactyly, syndactyly, or positional defects, and a change in the rate of one type(e.g., radial reduction defects) can easily be hidden by the large numbers of more common defects.A problem is that the pathogenesis of specific defects is not always agreed upon and may evenvary for the same malformation. A small bowel atresia, for instance, may be the result of a veryearly disturbance in gut development, the result of faulty secondary canalization of the gut rudiment,or the result of an ischemic insult perhaps occurring rather late in development. A transverse limbreduction defect may be caused by an early disturbance in limb development, may be the secondaryconsequence of a vascular accident, or may occur as the result of a so-called amniotic constrictionband. It is therefore not possible to set up a strict categorization of congenital malformations thatmirrors pathogenesis, but it must be done in a more intuitive way. Nevertheless, if the subdivisionis carried too far, the number of infants with malformations in each subgroup becomes so low thatanalysis is meaningless.3. Mutagenesis and TeratogenesisAn environmental factor may cause congenital malformations by a mutagenic process affectinggerm cells, resulting either in DNA point mutations or in chromosomal anomalies (e.g., nondisjunctionresulting in trisomy or breaks resulting in translocation). To cause congenital malformations,mutagenesis usually has to affect the germ cell genome. This means that an effect can beseen from paternal or maternal exposures and that most likely the event has occurred beforeconception. It could also occur during very early embryonic cell divisions. Mutagenic events duringembryonic or fetal development are more likely to cause malignancy rather than malformation. In© 2006 by Taylor & Francis Group, LLC