This is one of the most frequent and also most appalling congenital malformations of the brain. Its incidence is 0.1 to 0.7 per all 1,000 births and females predominate in ratios ranging between 3:1 and 7:1 in different series. The concordance rate is low, both in identical and fraternal twins, but the incidence of the malformation is, nonetheless, several times the expected rate if one child in the sibship has been affected. Anencephaly has also been more frequent in certain geographic areas, for example, Ireland, for which various explanations of population genetics or environmental exposure have been postulated.
Missing in cases of anencephaly are large portions of scalp, cranial bones, and brain, including both cerebral cortex and white matter. All that remains is a hemorrhagic nubbin of nerve, glial, and connective tissue. Brainstem, cerebellum, and spinal cord are present but often, they too are malformed, as are the heart and other organs (15 to 40 percent of cases). In anencephalics who survive for a few days (65 percent die in utero and almost 100 percent before the end of the first postnatal week), startle reactions may be observed, as well as movements of limbs, spontaneous respirations, pupillary light reactions, ocular movements, and corneal reflexes. In a few, avoidance reactions, crying, and feeding reflexes can be elicited, indicating that only the rudimentary brain structures are required for these functions.
This condition, or a related one, can be anticipated if the mother’s serum levels of alpha-fetoprotein and acetylcholinesterase are elevated—even more reliably anticipated if they are elevated in the amniotic fluid. Abnormal tests usually lead to ultrasonograph imaging of the fetus. Hydramnios is common.
The causes of anencephaly are multiple and include chromosomal abnormalities, maternal hyperthermia, and, deficiencies of folate, zinc, and copper (see Medical Task Force on Anencephaly). Of these, there is evidence that supplemental intake of folic acid during the first trimester of pregnancy (i.e., from the time of conception) reduces the incidence of anencephaly and of myelomeningocele. Additional comments on anencephaly are given further on in this chapter in the section on “Dysraphism, or
Rachischisis” (lack of fusion of the neural tube).
Lissencephaly (Agyria), Holoprosencephaly, and
Included under this heading are several forms of defects of cerebral sulcation. In the lissencephalies, cortical convolutions may be absent altogether and there is morphologic evidence of several types of neuroblast deficiency. Such cases are of particular interest to neonatologists because of their associated physical abnormalities, though the degree of impairment of neurologic function seldom allows longevity. Seizures, poor temperature regulation, failure to accept nourishment, and apneic attacks combine to shorten life.
The failures of sulcation vary in severity. Neurons may fail to form or to migrate along glial projections to reach the more superficial layers of the cortex (a condition called in the past, Bielschowsky type); or the cortex, meninges, and eyes may fail to differentiate normally except for the dentate gyrus and hippocampus (Walker-Warburg type); or there may be other more minor focal derangements of cortical migrations and laminations with heterotopias of neurons in the white matter.