Neuropathology Of Down's Syndrome
Down’s syndrome is the most commonly identified cause of mental retardation occurring in 1 out of 700 live births. In addition to mental deficiency, characteristics of the disease include epicanthic folds of the eyes, flattened facial features, unusual palm creases, short stature, open mouth, protruding tongue and poor posture. A twenty-two to fifty fold increase in risk of the development of leukemia along with congenital heart defects in forty percent of these individuals is also seen. The increased level of purines often found can lead to mental retardation itself. Neurological impairment and immune system deficiencies make these individuals more susceptible to infection. Also noted are increased risk for cataract development and vision impairment due to defects in the lenses of the eyes.
Evidence for the disease can be found as far back as the nineteenth century with many theories for the etiology of the disease. Early hypotheses include links to endocrine gland malfunction, tuberculosis, syphilis and "uterine exhaustion". The idea of uterine exhaustion was based on the observation that many children with Downs Syndrome (DS) tended to be the last born members of large families. This was later accounted for as mere coincidence. The first formal reference to the anomaly came in 1866 in England by a physician at the Earlewood Asylum noting the distinct physical characteristics of this group of individuals. In the 1930’s, Adrian Bleyer hypothesized that the condition was caused by a failure of the chromosomes to separate but could provide no proof for this since an accurate human chromosome count had not yet been obtained by anyone. The correct number of 46 chromosomes was obtained in Sweden in the 1950’s, and shortly thereafter a total of 47 was verified in a Down’s individual confirming non-disjunction as the mutation occurring. When non-disjunction occurs, the chromatics do not separate so one of the daughter cells receives two chromatics and the other none. The daughter cell in which the chromatic is absent will die and the other will receive a third copy upon fertilization resulting in a variety of defects. This non-disjunction can occur during anaphase I or anaphase II when the chromatics are pulled to opposite poles by the spindle fibers of the centromere. Trisomy, having three copies of a chromosome, most commonly occurs in chromosome 21, the smallest of the 23 human chromosomes. The process showing normal meosis, non-disjunction occurring in meosis I and non-disjunction occurring in meosis II is illustrated on the following figure.
In five percent of Down’s syndrome cases, translocation rather than non-disjunction is the cause. In this instance, only part of chromosome 21 is tripled as a portion of one adheres to another. A fragment of 21 is attached most often to chromosome 13, 14, 15, 21 or 22 and appears with a normal chromosome 21 from the other gamete. Again upon fertilization, a...