Intellectual Disability Workup

Updated: Apr 19, 2016
  • Author: Ari S Zeldin, MD, FAAP, FAAN; Chief Editor: Amy Kao, MD  more...
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Laboratory Studies

The examiner must determine the nature and extent of the laboratory investigation following a history and physical examination. Recommendations have been made by both the American Academy of Pediatrics [27] and the American Academy of Neurology [5] .

Availability of genetic testing, and thus recommendations for work-up, are changing rapidly. Chromosomal microarray and new sequencing techniques have revolutionized genetic testing. [28]

Array-based comparative genetic hybridization (CGH) or "microarray" is increasingly used in the evaluation of MR/ID and should be considered in the work-up of all children with MR/ID either after or as first-line instead of high-resolution karyotype and fragile-X testing (see below). The yield may be as high as 20%; however, a high false-positive rate can also confound interpretation. [29, 30, 31, 28]

High-resolution karyotype (at the 650 band level of resolution at least) should be completed in all children with MR/ID. [27] Chromosomal abnormalities (trisomy 21 and others) may account for as many as 50% of those affected by severe to profound MR/ID.

Fragile X testing (ie, DNA analysis of the FraX promoter region) should be ordered in all children with MR/ID. [5] In the postpubertal period, the clinical manifestations of Fragile X syndrome are likely to be readily apparent, such that DNA analysis can be ordered with more selectivity in this population. Sex chromosome aneuploidy is seen in as many as 5% of children with mild MR/ID or learning disabilities.

FISH probes are ordered as clinically indicated, as follows:

  • Prader-Willi/Angelman syndrome

  • Smith-Magenis syndrome

  • CATCH 22

  • Williams syndrome

  • Wolf-Hirschhorn syndrome

  • Cri du chat syndrome

  • Langer-Giedion (trichorhinophalangeal) syndrome

  • Miller-Dieker syndrome

Given their low yield, metabolic labs are not routinely ordered unless clinically indicated or newborn metabolic screen was not done or results are not available. [5]

  • Plasma amino acids (aminoacidopathies)

  • Urinary organic acids (organic acidopathies)

  • Urinary mucopolysaccharides and oligosaccharides (mucopolysaccharidoses)

  • Plasma 7-DHC (Smith-Lemli-Opitz syndrome)

  • Thyroid function tests

  • Very-long-chain fatty acids (peroxisomal disorders)

  • Creatine kinase (in the assessment of profound central hypotonia versus myopathy)

Consider lead testing in children with risk factors.


Imaging Studies

See the list below:

  • Brain MRI

    • Brain imaging should be conducted in any child with global developmental delays or MR/ID. The yield will be higher in the setting of an abnormal neurologic examination (eg, microcephaly, focal neurologic finding and/or facial dysmorphisms). [5]

    • Brain MRI is generally preferred over CT scan because the former has greater resolution and enhanced detection of abnormalities in the progression and timing of myelination, demyelination, and heterotopic gray matter.

  • Head CT scan: This is the preferred imaging study for calcifications that may be identified with TORCH infections (ie, toxoplasmosis, other infections, rubella, CMV, herpes simplex), when tuberous sclerosis is suspected, or if craniosynostosis is a concern.

  • Skeletal films: These assist with the phenotypic description, syndrome characterization, and assessment of growth.


Other Tests

Detailed assessment by a licensed professional is necessary to confirm the diagnosis of MR/ID. Some of the most commonly used tests in children include the following:

  • Bayley Scales of Infant Development

    • Normalized for ages 2-49 months

    • Subtest scores for receptive and expressive language, gross motor, fine motor, cognitive/problem-solving ability, and sustained attention

  • Stanford-Binet Intelligence Scale

    • Normalized for ages 2 years to 23 years

    • Fifteen subtests for assessment of 4 key areas of cognitive proficiency: verbal reasoning, abstract/visual reasoning, quantitative memory, and short-term memory

  • Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R)

    • Normalized for ages 3 years to 7.25 years

    • Twelve subtests for assessment of verbal and nonverbal intelligence

  • Wechsler Intelligence Scale for Children–IV (WISC-IV)

    • For ages 6 years to 16 years, 11 months

    • Verbal and nonverbal intelligence scores derived from 12 subtests

  • Vineland Adaptive Behavior Scales-II

    • For neonates to adults

    • Measures ability to perform daily activities required for personal and social sufficiency; adaptive or functional behaviors rated by interviewing the patient or parent/caregiver

    • Deficiencies in at least 2 areas of adaptive skills required to meet the MR/ID diagnostic criteria

Electrophysiologic studies

  • Auditory evoked potentials in the context of audiologic assessment

  • Visual evoked potentials in cases of profound delay and suspected cortical blindness

  • EEG is not recommended as part of the routine work-up of MR/ID unless the history is suggestive of seizures or a specific epileptic syndrome. [5]


Histologic Findings

Pathologic analysis of cortical tissue by the Golgi method in the 1970s suggested that in cases of profound, unclassified MR, dendritic spines were decreased and/or had immature morphology. These findings have been confirmed in cortical autopsy material from individuals with Down syndrome and FraX. Dendritic spine morphology is related directly to the intradendritic microtubular components and their organization.

Microtubules in dendrites of cortical neurons often are fragmented or in disarray in cases of developmental failure. In contrast, in some neuronal storage diseases associated with impaired cognition, dendritic spines are sprouted exuberantly beyond the developmental period and in ectopic locations. A relationship is implied, then, between dendritic spine morphology and number and cognitive development in the human.