eMedicine Specialties > Neurology > Pediatric Neurology
Mental Retardation: Differential Diagnoses & Workup
Updated: Apr 17, 2006
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Autism/pervasive developmental disorder
CNS trauma
Environmental deprivation
Major sensory deficits (eg, deafness, blindness)
Malnutrition
Mitochondrial cytopathies
Workup
Laboratory Studies
- No laboratory and/or radiologic investigation is routine in MR. The examiner must determine the nature and extent of the laboratory investigation following a history and physical examination.
- DNA analysis of the FraX promoter region should be ordered on all prepubertal males with MR, particularly if autistic features are noted. In the postpubertal period, the clinical manifestations of FraX are likely to be readily apparent, such that DNA analysis can be ordered with more selectivity in this population.
- Karyotype at the 500 band level of resolution (at least) should be considered in all children with MR.
- Chromosomal abnormalities (Tri 21 and others) may account for as many as 50% of those affected by severe to profound MR.
- Sex chromosome aneuploidy is seen in as many as 5% of children with mild MR 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
- Metabolic labs are ordered only as clinically indicated.
- 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)
Imaging Studies
- Brain MRI
- Brain imaging should be conducted in any child with developmental delay and abnormal findings on neurologic examination, including abnormalities of head size and/or facial dysmorphisms.
- Brain MRI generally is 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 psychological assessment by a licensed psychologist is necessary to confirm the diagnosis of MR. Some of the most commonly used psychological tests in children include the following:
- Bayley Scales of Infant Development
- Normalized for ages 2-30 months
- Subtest scores for receptive and expressive language, nonverbal 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
- For neonates to adults
- Measures ability to perform daily activities required for personal and social sufficiency; adaptive or functional behaviors rated by interviewing the child's guardian
- Deficiencies in at least 2 areas of adaptive skills required to meet the MR diagnostic criteria
- Bayley Scales of Infant Development
- Electrophysiologic studies
- EEG, if clinically warranted
- Auditory evoked potentials in the context of audiologic assessment
- Visual evoked potentials in cases of profound delay and suspected cortical blindness
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.
More on Mental Retardation |
| Overview: Mental Retardation |
 Differential Diagnoses & Workup: Mental Retardation |
| Treatment & Medication: Mental Retardation |
| Follow-up: Mental Retardation |
| References |
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References
Ahn KJ, Jeong HK, Choi HS. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis. Jan 30 2006;[Medline].
Amir RE, Van den Veyver IB, Wan M. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpG-binding protein 2. Nat Genet. Oct 1999;23(2):185-8. [Medline].
Autti-Ramo I, Fagerlund A, Ervalahti N. Fetal alcohol spectrum disorders in Finland: Clinical delineation of 77 older children and adolescents. Am J Med Genet A. Jan 15 2006;140(2):137-43. [Medline].
Capute AJ, Accardo PJ. Developmental Disabilities in Infancy and Childhood. Vol 1 and 2. Baltimore: Paul H Brookes;1996: 1-619 and 1-521.
Doheny KF, McDermid HE, Harum K. Cryptic terminal rearrangement of chromosome 22q13.32 detected by FISH in two unrelated patients. J Med Genet. Aug 1997;34(8):640-4. [Medline].
Flint J, Wilkie AO, Buckle VJ. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. Feb 1995;9(2):132-40. [Medline].
Greenberg F, Lewis RA, Potocki L. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2). Am J Med Genet. Mar 29 1996;62(3):247-54. [Medline].
Gripp KW, Lin AE, Stabley DL. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am J Med Genet A. Jan 1 2006;140(1):1-7. [Medline].
Kaufmann WE, Abrams MT, Chen W. Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X syndrome. Am J Med Genet. Apr 2 1999;83(4):286-95. [Medline].
Kirchhoff M, Gerdes T, Brunebjerg S. Investigation of patients with mental retardation and dysmorphic features using comparative genomic hybridization and subtelomeric multiplex ligation dependent probe amplification. Am J Med Genet A. Dec 15 2005;139(3):231-3. [Medline].
Mao R, Wang X, Spitznagel EL. Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart. Genome Biol. 2005;6(13):R107. [Medline]. [Full Text].
Medina AE, Krahe TE, Ramoa AS. Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci. Jan 18 2006;26(3):1057-60. [Medline].
Miyake N, Shimokawa O, Harada N. BAC array CGH reveals genomic aberrations in idiopathic mental retardation. Am J Med Genet A. Feb 1 2006;140(3):205-11. [Medline].
Reiss S, Aman MG. Psychotropic Medications and Developmental Disabilities: The International Consensus Handbook. The Ohio State University Nisonger Center. 1998;1-355.
Richardson SA, Koller H. Twenty-Two Years. Cambridge, MA: Harvard University Press. 1996;1-328.
Tassabehji M, Metcalfe K, Fergusson WD. LIM-kinase deleted in Williams syndrome [letter]. Nat Genet. Jul 1996;13(3):272-3. [Medline].
Volkmar FR, Lewis M. Mental Retardation: Child and Adolescent Psychiatric Clinics of North America. Philadelphia: WB Saunders Company. 1996;5:769-993.
Further Reading
Keywords
cognitive impairment, intelligence quotient, IQ less than 70, learning disability, Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Smith-Magenis syndrome, CATCH 22 (22q11 deletion) syndrome, DiGeorge syndrome, velocardiofacial syndrome, Williams syndrome, Wolf-Hirschhorn syndrome, Langer-Giedion syndrome, Miller-Dieker syndrome, tuberous sclerosis, Rubinstein-Taybi syndrome, Coffin-Lowry syndrome, Rett syndrome, Smith-Lemli-Opitz syndrome, fetal alcohol syndrome, fetal alcohol effects, cretinism, congenital hypothyroidism, congenital cytomegalovirus, congenital rubella, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, traumatic brain injury, shaken baby syndrome, meningitis
