This broad heading subsumes a wide diversity of both developmental
malformations and diseases acquired during the intrauterine or early
neonatal periods of life. They number in the hundreds according
to the tabulation of Dyken and Krawiecki although many, if not most,
are rare. Taxonomically, they make up two broad categories. The
first includes unrelated genetic pathologic processes, some of which
originate in germ line abnormalities, including triplication, deletion, and
translocations of chromosomes, and probably some are inherited on
a polygenic basis. A remarkable accomplishment has been the identification
in the past several years of specific gene defects that give rise
to a number of these brain malformations. The second category comprises
a variety of noxious and infectious agents acting at different times
on the immature nervous system during the embryonal, fetal, and
perinatal periods of life.
It would be intellectually satisfying if all the states that
originate in the intrauterine period could be separated strictly
into genetic or nongenetic forms, but in most instances the biologic
information and the pathologic changes in the brain at this early
age do not allow such a division. For example, among the many diseases
in which the neural tube fails to close (rachischisis), more than
one member of a family may be affected but it cannot be stated whether
a genetic factor is operative or an exogenous factor, such as folic
acid deficiency, has acted on several members during a succession
of pregnancies of one mother. Even what appears to be an outright
malformation of the brain may be no more than a reflection of the
timing of an exogenous process that has affected the nervous system
early in the embryonal period, derailing later processes of development. Teratology,
the scientific study of malformations, is replete with such examples.
Several points should be noted regarding the frequency of developmental
disorders; Smith (see Jones) has pointed out that a single malformation,
usually of no clinical significance, occurs in 14 percent of newborns.
Two malformations appear in 0.8 percent of newborns, and in this
group, a major defect is 5 times more frequent than in the normal
population. Three or more malformations are found in 0.5 percent
of newborns, and in this latter group, more than 90 percent have
one or more major abnormalities that seriously interfere with viability
or physical well-being. The figures for major congenital malformations
compiled by Kalter and Warkany are comparable but somewhat higher.
What is most important for the neurologist is the fact that the
nervous system is involved in most of infants with major malformations.
Indeed, approximately 40 percent of deaths during the first postnatal
year are in some manner related to prenatal malformations of the
central nervous system.
Certain principles are applicable to the entire group of developmental
brain disorders. First, as just noted, the abnormality
of the nervous system is frequently accompanied by an abnormality
of some other structure or organ (eye, nose, cranium, ...