Comprehensive evaluation of the child with intellectual disability or global developmental delays

Abstract

Global developmental delay and intellectual disability are relatively common pediatric conditions. This report describes the recommended clinical genetics diagnostic approach. The report is based on a review of published reports, most consisting of medium to large case series of diagnostic tests used, and the proportion of those that led to a diagnosis in such patients. Chromosome microarray is designated as a first-line test and replaces the standard karyotype and fluorescent in situ hybridization subtelomere tests for the child with intellectual disability of unknown etiology. Fragile X testing remains an important first-line test. The importance of considering testing for inborn errors of metabolism in this population is supported by a recent systematic review of the literature and several case series recently published. The role of brain MRI remains important in certain patients. There is also a discussion of the emerging literature on the use of whole-exome sequencing as a diagnostic test in this population. Finally, the importance of intentional comanagement among families, the medical home, and the clinical genetics specialty clinic is discussed.

FIGURE 1

Diagnostic process and care planning. Metabolic test 1: blood homocysteine, acylcarnitine profile, amino acids; and, urine organic acids, glycosaminoglycans, oligosaccharides, purines, pyrimidines, GAA/creatine metabolites. Metabolic test 2 based on clinical signs and symptoms. FH, family history; MH, medical history; NE, neurologic examination; PE, physical and dysmorphology examination.