VISCEROMEGALYNiemann-PickInfantile GaucherPompeFarberSandhoff (some cases)Later, mucolipidosis and   polysaccharidosesPURELY NEUROLOGIC DISEASESPredominantly gray matterTay-SachsSandhoffGM1 gangliosidosisNeuronal ceroid lipofuscinosesLeighAlexanderNeuroaxonal dystrophySpongy degeneration   (Canavan)Pelizaeus-MerzbacherAdrenoleukodystrophyGloboid-body (Krabbe)Metachromatic leukodystrophyPredominantly white matter
Developmental Diseases of the
This broad heading subsumes a large number of both genetically driven developmental malformations and diseases acquired during 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 categories. The first includes specific gene defects, either mutations, deletions, or duplications of parts of genes (copy number variation), or single nucleotide polymorphisms that give rise to developmental aberrations or delays. The second category comprises a variety of environmental and infectious agents acting at different times on the immature nervous system during embryonal, fetal, and perinatal periods of life.
Several points should be noted regarding the frequency of malformations. Jones, in the Smith monograph, has pointed out that a single minor 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 five 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 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 malformations. First, the abnormality of the nervous system is frequently accompanied by an abnormality of some other structure or organ (eye, nose, cranium, spine, ear, and heart), which relates them chronologically to a certain period of embryogenesis. Conversely, the presence of these malformations of nonnervous tissues suggests that an associated abnormality of the nervous system is developmental in nature. For example, the conjunction of cardiac, limb, gut, and bladder abnormalities with a neurologic disorder indicates the time at which the insult takes place: cardiac abnormalities occur between the fifth and sixth week; extroversion of the bladder at less than 30 days; duodenal atresia, before 30 days; syndactyly, before 6 weeks; meningomyelocele, before 28 days; anencephaly, before 28 days; cleft lip, before 36 days; syndactyly, cyclopia, and holoprosencephaly, before 23 days. Each is discussed in this chapter. This principle is not inviolable; in certain maldevelopments of the brain that must have originated in the embryonal period, all other organs are normal. One can assume that the brain was more vulnerable than any other organ to prenatal as well as natal influences. Perhaps this occurs because the nervous system, of all organ systems, requires the longest time for its development and maturation, during which it is susceptible to disease. Low birth weight and gestational age, indicative of premature birth, increase the risk of cognitive or sensory developmental delay, seizures, and cerebral palsy.