In most of the above-described cerebral dysplasias, the cranium and brain are small, but there is also a primary form of hereditary microcephaly, called microcephaly vera, in which the head is astonishingly reduced in size (circumference less than 45 cm in adult life—i.e., 5 standard deviations below the mean). In contrast, the face is of normal size, the forehead is narrow and recedes sharply, and the occiput is flat. The brain often weighs less than 300 g (normal adult range: 1,100 to 1,500 g) and shows only a few primary and secondary sulci. The cerebral cortex is thick and unlaminated and grossly deficient in neurons. There has been, of course, current interest in maternal Zika infection as cause.
A few cases have an associated cerebellar hypoplasia or an infantile muscular atrophy. Stature is usually moderately reduced. Such individuals can be recognized at birth by their anthropoid appearance and later by their lumbering gait, severe cognitive impairment, and lack of communicative speech. Vision, hearing, and cutaneous sensation are spared. In one of the cases studied by our colleagues, laborious effort using operant conditioning made it possible to teach the patient the shapes of simple figures. Skull films show that the cranial sutures are present, as are convolutional markings on the inner table.
Lesser degrees of microencephaly have been associated with progressive motor neuron disease and degeneration of the substantia nigra (Halperin et al). Evrard and associates have described another rare type of microcephaly, which they call “radial microbrain.” The sulcal pattern is normal, and neuronal arrangements in the cerebral cortex are normal as well. The defect appears to be in the small number of neurons that are generated, not in their migration.
Disorders of the Pial Surface
This category of maldevelopment is characterized by inappropriate migration of neurons to the pial surface, leading to a nodularity of the surface described as a cobblestone appearance. In the three disorders with this pathologic finding, the clinical picture is one of developmental delay conjoined with congenital muscular dystrophy. Three identified gene defects are thought to alter the glycosylation of critical proteins in the brain and in skeletal muscle. These genes include the gene fukutin in Fukuyama muscular dystrophy (see “Congenital Muscular Dystrophy” in Chap. 45), the POMGNT1 gene in muscle-eye-brain disease, and the POMT1 gene in Walker-Warburg syndrome, as summarized in Table 37-3.
Combined Cerebral, Cranial, and Somatic Abnormalities
There are so many cerebrosomatic anomalies that one can hardly retain visual images of them, much less recall all the physicians’ names by which they are known. There is great advantage in grouping these anomalies according to whether the extremities, face, eyes, ears, and skin are associated with a cerebral defect. The sheer number and variety of these anomalies permit only an enumeration of the more common ones and their most obvious physical characteristics. Unfortunately, apart from certain genetic linkages, no useful leads as to their origin have been forthcoming. Of necessity, one turns to atlases, one of the most thorough of which was compiled by Holmes and colleagues and is based on clinical material drawn in large part from the Fernald School and Eunice K. Shriver Center in Massachusetts. The reader may also turn to the texts by Gorlin and colleagues and by Jones for specific information. The older Ford’s Diseases of the Nervous System in Infancy, Childhood, and Adolescence is still a valuable reference, as is Jablonski’s Dictionary of Syndromes and Eponymic Diseases.
The Syndactylic–Craniocerebral Anomalies (Acrocephalosyndactyly)