Mental Retardation Workup

  • Author: Ari S Zeldin, MD, FAAP; Chief Editor: Amy Kao, MD   more...
 
Updated: Nov 10, 2010
 

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[22] and the American Academy of Neurology[23] .
  • DNA analysis of the FraX promoter region should be ordered on all children with MR/ID.[23] 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 650 band level of resolution (at least) should be completed in all children with MR/ID.[22]
  • Chromosomal abnormalities (trisomy 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.
  • Array-based comparative genetic hybridization (CHG) or microarray is being increasingly used in the evaluation of MR/ID and should be considered in the workup after routine cytogenic studies have been done. The yield may be as high as 10%; however, a high false positive rate can also confound interpretation.[24, 25]
  • 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 availble.[23]
    • 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)
Next

Imaging Studies

  • 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).[23]
    • 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.
Previous
Next

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.[23]
Previous
Next

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.

Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Ari S Zeldin, MD, FAAP  Senior Clinical Fellow/Clinical Instructor in Autism and Neuro-Developmental Disorders, Division of Pediatric Neurology, Department of Neurosciences, University of California, San Diego, School of Medicine

Ari S Zeldin, MD, FAAP is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, and Child Neurology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Alicia T F Bazzano, MD, MPH  Consulting Faculty, Division of Pediatric Emergency Medicine, Harbor/UCLA Medical Center; Attending Staff, Department of Emergency Medicine, Children's Hospital Los Angeles; Chief Physician, Westside Regional Center

Alicia T F Bazzano, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Public Health Association, and American Society for Bioethics and Humanities

Disclosure: Nothing to disclose.

Specialty Editor Board

Beth A Pletcher, MD  Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey

Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Kenneth J Mack, MD, PhD  Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD  Attending Neurologist, Children's National Medical Center, Washington DC

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

References

  1. Schroeder S, Gerry M, Gertz G, Velasquez F. Final Project Report: Usage of the Term "Mental Retardation:" Language, Image and Public Education. Social Security Administration; June 2002. [Full Text].

  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision. Washington DC: American Psychiatric Association; 2000.

  3. American Psychiatric Association. APA DSM-5 Development: Proposed Revision: Mental Retardation. American Psychiatric Association DSM-5 Development. Available at http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=384. Accessed March 20, 2010.

  4. Birch HG, Richardson SA, Baird D, Horobin G, Illsley R. Mental Subnormality in the Community: A Clinical and Epidemiologic Study. Baltimore: Williams & Wilkins; 1970.

  5. Patja K, Mölsä P, Iivanainen M. Cause-specific mortality of people with intellectual disability in a population-based, 35-year follow-up study. J Intellect Disabil Res. Feb 2001;45:30-40. [Medline].

  6. Rutter M, Graham P. Epidemiology of psychiatric disorder. In: Rutter M, Tizard J, Whitemore P. Education, Health and Behavior. London, England: Longman Group; 1970:178-201.

  7. Strauss D, Eyman RK. Mortality of people with mental retardation in California with and without Down syndrome, 1986-1991. Am J Ment Retard. May 1996;100(6):643-53. [Medline].

  8. [Guideline] Moeschler JB, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. Jun 2006;117(6):2304-16. [Medline]. [Full Text].

  9. Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. Jul 16 2003;290(3):337-44. [Medline].

  10. Dawson G, Munson J, Webb SJ, Nalty T, Abbott R, Toth K. Rate of head growth decelerates and symptoms worsen in the second year of life in autism. Biol Psychiatry. Feb 15 2007;61(4):458-64. [Medline].

  11. Kenneth Lyons Jones. Smith's Recognizable Patterns of Human Malformations. 6. Elsevier Saunders; 2006:160-161.

  12. 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].

  13. 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].

  14. Tassabehji M, Metcalfe K, Fergusson WD. LIM-kinase deleted in Williams syndrome [letter]. Nat Genet. Jul 1996;13(3):272-3. [Medline].

  15. Verhoeven WM, Tuinier S, Kuijpers HJ, Egger JI, Brunner HG. Psychiatric Profile in Rubinstein-Taybi Syndrome. A Review and Case Report. Psychopathology. Nov 20 2009;43(1):63-68. [Medline].

  16. Marques Pereira P, Schneider A, Pannetier S, Heron D, Hanauer A. Coffin-Lowry syndrome. Eur J Hum Genet. Nov 4 2009;[Medline].

  17. 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].

  18. Axelrad ME, Schwartz DD, Fehlis JE, Hopkins E, Stabley DL, Sol-Church K, et al. Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome. Am J Med Genet A. Dec 2009;149A(12):2666-72. [Medline].

  19. 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].

  20. 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].

  21. Mann JR, McDermott S, Barnes TL, Hardin J, Bao H, Zhou L. Trichomoniasis in pregnancy and mental retardation in children. Ann Epidemiol. Dec 2009;19(12):891-9. [Medline].

  22. Moeschler JB, Shevell M,. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. Jun 2006;117(6):2304-16. [Medline].

  23. Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology. Feb 11 2003;60(3):367-80. [Medline].

  24. Liang JS, Shimojima K, Yamamoto T. Application of array-based comparative genome hybridization in children with developmental delay or mental retardation. Pediatr Neonatol. Dec 2008;49(6):213-7. [Medline].

  25. Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JP, Burton H. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. Mar 2009;11(3):139-46. [Medline].

  26. Bazzano AT, Zeldin AS, Diab IR, Garro NM, Allevato NA, Lehrer D. The Healthy Lifestyle Change Program: a pilot of a community-based health promotion intervention for adults with developmental disabilities. Am J Prev Med. Dec 2009;37(6 Suppl 1):S201-8. [Medline].

  27. Kishnani PS, Sommer BR, Handen BL, Seltzer B, Capone GT, Spiridigliozzi GA, et al. The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am J Med Genet A. Aug 2009;149A(8):1641-54. [Medline].

  28. Rueda JR, Ballesteros J, Tejada MI. Systematic review of pharmacological treatments in fragile X syndrome. BMC Neurol. Oct 13 2009;9:53. [Medline]. [Full Text].

  29. Ellis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R, et al. Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial. BMJ. Mar 15 2008;336(7644):594-7. [Medline]. [Full Text].

  30. 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].

  31. Capute AJ, Accardo PJ. Developmental Disabilities in Infancy and Childhood. Vol 1 and 2. Baltimore: Paul H Brookes;1996: 1-619 and 1-521.

  32. Developmental surveillance and screening of infants and young children. Pediatrics. Jul 2001;108(1):192-6. [Medline].

  33. 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].

  34. 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].

  35. 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].

  36. 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].

  37. MASSACHUSETTS DEPARTMENT OF DEVELOPMENTAL SERVICES. Massachusetts Department of Developmental Services Annual Health Screening Recommendations. Available at http://www.mass.gov/Eeohhs2/docs/dmr/health_screening_checklist.pdf. Accessed April 1, 2010.

  38. Rubin IL, Crocker AC. Medical care for children and adults with developmental disabilities. Second edition. Baltimore, MD: Paul H Brookes Publishing Co, Inc; 2006.

  39. 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].

  40. 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].

  41. Reiss S, Aman MG. Psychotropic Medications and Developmental Disabilities: The International Consensus Handbook. The Ohio State University Nisonger Center. 1998;1-355.

  42. Richardson SA, Koller H. Twenty-Two Years. Cambridge, MA: Harvard University Press. 1996;1-328.

  43. Volkmar FR, Lewis M. Mental Retardation: Child and Adolescent Psychiatric Clinics of North America. 5. Philadelphia: WB Saunders Company; 1996:769-993.

 
Previous
Next
 
Table 1. Intellectual disability categorization
Category IQ



score*



(SD below mean)



Proportion of MR/ID Educational level/adaptive skills Intensity of supports required Prevalence in total population
Mild50-55 to 70



(2-3)



85%Up to about 6th grade; vocationalIntermittent, especially under stress0.9-2.7%
Moderate35-40 to 50-55



(3-4)



10%up to about 2nd grade; unskilled or semi-skilled, supervisedLimited;



usually supervised



0.3-0.4%
Severe20-25 to 35-40



(4-5)



4%May learn words; elementary self-care skillsExtensive; closely supervised group or family home
Profound< 20-25 (>5)1%Little to no self-care skillsConstant aid and supervision
*IQ scores are considered +/-5 points due to measurement error.
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.