However, there is emerging information relating autosomal mutations, rather than X-linked ones, in genes that control synaptic function such as SYNGAP1, and non-dysmorphic developmental delay as detailed in the publication by Hamdan and coworkers. There are approximately 30 X-linked and 6 autosomal recessive genes associated with nonsyndromic developmental delay and more are sure to be found. Investigated from another perspective, de Ligt and colleagues sequenced the coding regions of over 21,000 genes in a series of 100 individuals with IQ below 50 and round that there were numerous de novo mutations that involved cerebral development of function. Together, all of the aforementioned genetic alterations, mutations, lesser polymorphisms and copy number variants, account for approximately 15 to 20 percent of cases of mild, moderate, and severe developmental delay and autism. Most are de novo mutations, making their discovery difficult. The challenge will be to elucidate the manner in which they disrupt cerebral development on a synaptic or subcellular level.
Infants should be considered at risk for developmental delay when there is a family history of developmental delay, low birth weight in relation to the length of gestation (small-for-date babies), marked prematurity, maternal infection early in pregnancy (especially rubella), and toxemia of pregnancy. In the first few months of life, certain of the behavioral characteristics described above are of value in predicting developmental delay. Prechtl and associates have found that a low Apgar score (especially at 5 min after delivery, Table 27-3), flaccidity, underactivity, and asymmetrical neurologic signs are the earliest indices of subnormality in the infant. Slow habituation of orienting reactions to novel auditory and visual stimuli and the presence of “fine motor deficits” (as previously discussed under “Delays in Motor Development”) are other early warnings of developmental delay.
In the first year or two of life, suspicion of developmental delay is based largely on clinical impression, but it should always be validated by psychometric procedures. Most pediatric neurologists use some of the criteria laid down by Gesell and Amatruda or the Denver Developmental
Screening Scale, from which a DQ is calculated.
For testing of preschool children, the Wechsler Preschool and Primary Scale of Intelligence is used, and for school-age children, the Wechsler Intelligence Scale for Children is preferred. IQ tests for preschoolers must be interpreted with caution, as they have had less predictive validity for school success than the tests that are used after 6 years of age. In general, however, normal scores for age on any of these tests essentially eliminate developmental delay as a cause of poor school achievement and learning disabilities; special cognitive defects may, however, be revealed by low scores on particular subtests. Developmentally delayed children not only have low scores but exhibit more scatter of subtest scores. Also, like demented adults, they generally achieve greater success with performance than with verbal items. It is essential that the physician know the conditions of testing, for poor scores may be due to fright, inadequate motivation, lapses in attention, dyslexia, or a subtle auditory or visual defect rather than a developmental lag.
The EEG, in addition to exposing asymptomatic seizure activity, shows a high incidence of other abnormalities in the developmentally delayed child. Presumably this is because of a greater degree of immaturity of the cerebrum at any given age. However, a normal EEG is not infrequent and of relatively little help. Moreover, CT and MRI have been unhelpful in revealing abnormalities in this group of children.