In planning the approach to diagnosis of developmental disability and seizures in a child, it is useful to consider the major categories of genetic and hereditary metabolic disease. These will guide the types and sequence of testing. Table: Assessment of Seizures and Developmental Disability

First, the clinician should determine whether a nongenetic cause could explain the symptoms. These may include:

  • recent trauma
  • child abuse with shaking and rupture of bridging veins
  • brain tumor
  • vascular malformation

Therefore, a brain imaging study is high on the list of useful tests whenever a progressive disorder is being evaluated. An MRI scan might reveal a neuronal migration disorder, a leukodystrophy, an abnormality of the basal ganglia (e.g., striatal necrosis), or calcifications. If a leukodystrophy is found, magnetic resonance spectroscopy (MRS) might be used to demonstrate the elevation in N-acetyl aspartic acid characteristic of Canavan’s disease. In considering cerebral dysgenesis, we look for pachygyria, schizencephaly, polymicrogyria, heterotopias, and other forms of cortical dysplasia.10

Next, screening blood tests are performed to determine the complete blood cell count and electrolytes, calcium, magnesium, glucose, lactic acid, pyruvic acid, ammonia, and biotinidase levels. Assessment of blood amino acids, very long-chain fatty acids, or peroxisomal diseases and chromosomes (fluorescent in situ hybridization analysis) for Angelman’s syndrome also may be undertaken, depending on the clinical findings. If a disorder of fatty acid oxidation is being considered, acylcarnitines are evaluated.

Urine can be examined for its content of N-acetyl aspartate (Canavan’s disease), mucopolysaccharides (Sanfilippo’s syndrome), sialyloligosaccharides (sialidosis), and organic acids.

A skin biopsy may be obtained to examine dermal nerves under the electron microscope for storage, as in the lysosomal diseases, Lafora’s disease, and neuroaxonal dystrophy, as well as for fibroblast cell culture to conduct enzymatic and DNA mutation analyses.

A child’s electroencephalogram (EEG) may be abnormal even before the clinical appearance of seizures, as in Rett syndrome and Angelman’s syndrome. For this reason, we examine the EEG as part of our routine study of the child with cognitive delay.

Other neurophysiologic tests that can help to localize seizure pathology include evoked potentials, electromyography, and the study of sensory and motor nerve conduction.

Adapted from: Kolodny, EH. Metabolic and genetic disorders. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;17–22. 
With permission from Elsevier (

Reviewed By: 
Steven C. Schachter, MD
Saturday, May 1, 2004