Members of both groups of these mildly delayed individuals exhibit a number of noteworthy features that have medical and social implications. Although not overtly dysmorphic and having a normal or low-normal head circumference, they have a high incidence of minor congenital anomalies of the eyes, face, mouth, ears, and hands; they tend to be sickly, and the more severely affected among them have poor physiques and are often undersized. Difficult behavior occurs frequently, most often taking the form of poor self-control and aggressiveness, especially pronounced in children with temporal lobe epilepsy. Other behavioral disturbances are restlessness, repetitive activity, explosive rage reactions and tantrums, stereotyped play, and the seeking of sensory experiences in unusual ways. Pica (the compulsive ingestion of nonnutritive substances) is a problem between ages 2 and 4 years of age, but is also seen in normal, neglected children.
An endless debate is centered on matters of causation—whether this category of mild delay is the product of genetic influence or of societal discrimination and lack of training and education coupled with the effects of malnutrition, infections, or other exogenous factors. Surely both factors are at work, with the genetic being dominant for the reasons discussed above, although the relative importance of each has proved difficult to determine.
A pathologic basis for most cases of mild developmental delay has not been established and new methodologies, perhaps relating to neuronal connectivity, will be needed if the brains of these individuals are to be differentiated from normal children. Differences might be expected in terms of the number of neurons in thalamic nuclei and cortex, in dendritic–axonal connectivity, or in synaptic surfaces, elements that are not being assayed by the conventional techniques of tissue neuropathology. The observations of Huttenlocher, who found a sparsity of dendritic arborization in Golgi-Cox preparations, and of Purpura, who found an absence of short, thick spines on dendrites of cortical neurons and other abnormalities of dendritic spines, are first steps in this direction but require confirmation.
Genetic Aspects of Nonsyndromic
Sex linkage is a notable feature of some types of mild developmental delay. The fragile X syndrome, discussed later, is the most important of this group, predominating in males and accounting for approximately 10 percent of all cases of male developmental delay. These individuals may be physically normal except for large testicles. Renpenning and colleagues reported a series of 21 developmentally delayed males in three generations of a Canadian family, all free of any congenital malformations and with normal head size, and Turner and coworkers have described a similar Australian series. Other X-linked forms of developmental delay that have few or no dysmorphic features include the Partington, Lowe, Lesch-Nyhan, and Menkes syndromes and adrenoleukodystrophy, each with special characteristics in addition to developmental delay, as discussed in Chap. 36. Numerous other X-linked retardation syndromes with profound accompanying neurologic anomalies have been delineated; for example, the one caused by a mutation in the oligophrenin gene, in which there is epilepsy, and another involving cerebellar hypoplasia. The relationship of intelligence in general to the X chromosome is discussed in Chap. 20.