As alluded to earlier, the role of phase-contrast MRI of CSF flow around the foramen magnum in selecting patients for decompression is unknown. The treatment of an associated syringomyelia and other developmental abnormalities in this region is discussed further in Chap. 42 under “Intramedullary Syringomyelic Syndrome.” We are unable to comment on the use by a limited number of neurosurgeons of posterior fossa decompression for the treatment of chronic fatigue syndrome and all manner of other symptoms except to say that it is entirely illogical, even when a Chiari malformation is detected.
As mentioned in the introduction, a mid-twentieth-century discovery of outstanding significance was the recognition of a group of developmental anomalies of the brain and other organs associated with a demonstrable abnormality of the karyotype of autosomal and sex chromosomes. Jacobs and Lejeune in 1959 almost simultaneously were the first to note a triplication of the 21st chromosome in Down syndrome, and there followed the discovery of a number of other trisomies as well as deletions or translocations of other autosomal chromosomes and a lack or excess of one of the sex chromosomes. Such an event must take place sometime after the formation of the oocyte, during the long period when it lies fallow in the ovary or during the process of conception or germination and first cell divisions. Thus, all the cells in the embryo may carry the changed chromosome, or only some of them may carry it, the latter condition being called mosaicism.
The precise manner in which triplication or some other imperfection of a chromosome is able to derail the pathways of ontogenesis is a mystery. In some instances, a chromosomal imperfection may result from the lack of a gene or a distortion or fragmentation of an unstable gene, as in the fragile X syndrome. These germ line alterations are to be distinguished from acquired partial duplications and deletions of parts of genes that occur as acquired somatic mutations in many tumors and from variations in copy number of segments of genes that are emerging as possible explanations for a number of diseases such as autism.
Certain chromosomal abnormalities are incompatible with life, and it has been found that the cells of many abortuses and stillborns show abnormal karyotypes. Conversely, the organism may survive and exhibit any one of many syndromes, of which the following are the most frequent: (1) Down syndrome (trisomy 21); (2) one type of arrhinencephaly (trisomy 13, Patau syndrome); (3) trisomy 18 (Edwards syndrome); (4) cri-du-chat syndrome (deletion of short arm of chromosome 5); (5) monosomy 21; (6) ring chromosomes; (7) Klinefelter syndrome (XXY); (8) Turner syndrome (XO); (9) others (XXXX, XXX, XYY, YY, XXYY); (10) fragile X syndrome, in many surveys the most common identifiable form of inherited developmental delay; (11) Williams syndrome; and (12) Prader-Willi and Angelman syndromes. There are numerous less-frequent types, some of which are also discussed below because they have special neurologic interest. The overall frequency of chromosomal abnormalities in live births is 0.6 percent (see the review by Kalter and Warkany). For a comprehensive account of the chromosome-linked disorders the reader is referred to the article by Lemieux and for speculations on the nature of genetic causes of developmental delay, can be found in the article by Nokelainen and Flint.