Developmental Delay (DD) or Mental Retardation (MR) Testing

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Developmental Delay (DD) Testing Algorithm

Clinical Background

Developmental delay (DD) or mental retardation (MR) is a common cause of referral in pediatrics. DD is a subset of the developmental disabilities defined as neurocognitive impairments (IQ <70) as well as significant limitations in adaptive living skills (social, communication, work, leisure, daily living)

Epidemiology

Prevalence - 1-3% in the general population
Age - diagnosis generally <5 years of age
Sex - no predominance except in X-linked defects

Clinical Presentation

Neurocognitive impairment in addition to delays in 2 or more of the following:
- Social skills
- Community living
- Communication
- Home living
- Health
- Self-direction
- Work
- Leisure
Dysmorphic features present in >50%
- Mild dysmorphic features may be missed
Abnormal neurologic exam present in >40%
- Muscle weakness or hypotonia, spasticity, microcephaly, macroencephaly

See Also

Prader-Willi Syndrome - PWS

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Developmental Delay (DD) Testing Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Rett Syndrome (MECP2), Full Gene Analysis

ARUP #: 0051614

Methodology: Full Gene Sequencing/Multiplex Ligation Probe Amplification

Use:

Aid in determining etiology for GD/MR

Includes Rett syndrome (MECP2) full gene sequencing as well as deletion and duplication

Limitations:

Breakpoints of large deletions/duplications cannot be determined; deep intronic mutations will not be detected; analytical sensitivity may be compromised by rare primer site mutations

Test name: Rett Syndrome (MECP2), Full Gene Sequencing

ARUP #: 0051378

Methodology: Polymerase Chain Reaction/Sequencing

Use:

Aid in determining etiology for GD/MR

Limitations:

Deep intronic mutations and large deletions/duplications will not be identified; analytical sensitivity may be compromised by rare primer site mutations

Test name: Rett Syndrome (MECP2), Deletion and Duplication

ARUP #: 0051618

Methodology: Multiplex Ligation Probe Amplification

Use:

Aid in determining etiology for GD/MR

Limitations:

Breakpoints of large deletions/duplications cannot be determined; deep intronic mutations, single base pair substitutions and small deletions/duplications will not be detected; analytical sensitivity may be compromised by rare primer site mutations

Test name: Fragile X Syndrome, DNA Testing

ARUP #: 0040011

Methodology: Southern Blot/Polymerase Chain Reaction/Fragment Analysis

Use:

Aid in determining etiology for GD/MR

Limitations:

DNA analysis of the CGG repeat region is greater than 99% sensitive and 100% specific for diagnostic/carrier testing with the exception of a "gray zone" of 45-54 CGG repeats where carrier test results are inconclusive

Test name: Fragile X Syndrome, DNA Testing, Fetal

ARUP #: 0050543

Methodology: Southern Blot/Polymerase Chain Reaction/Fragment Analysis

Use:

Aid in determining etiology for GD/MR

Limitations:

Test name: Genomic Microarray, UARRAY Chip

ARUP #: 0040201

Methodology: Genomic Microarray

Use:

Aid in determining etiology for GD/MR

Limitations:

Detects unbalanced alternations of the genome >500 kb in size or affecting known microdeletion/microduplication syndromes

Will not detect balanced alternations, point mutations, or alterations of the genome not represented on the array

Test name: Chromosome Analysis, Peripheral Blood

ARUP #: 0097640

Methodology: Giemsa-Band Analysis

Use:

Aid in determining etiology for GD/MR

Test name: Chromosome Analysis, FISH-Metaphase

ARUP #: 0097615

Methodology: Fluorescence in situ Hybridization

Use:

FISH probes for specific microdeletion/microduplication syndromes must be specified; if no specific syndrome is in question, genomic microarray should be ordered instead for screening of multiple microdeletion/microduplication syndromes

Test name: Prader-Willi Syndrome

ARUP #: 0051116

Methodology: Methylation Sensitive Polymerase Chain Reaction/Fluorescent Monitoring

Use:

Aid in determining etiology for GD/MR

Test name: Angelman Syndrome

ARUP #: 0051113

Methodology: Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring

Use:

Aid in determining etiology for GD/MR

References

General References

Battaglia A, Bianchini E, Carey JC. Diagnostic yield of the comprehensive assessment of developmental delay/mental retardation in an institute of child neuropsychiatry. Am J Med Genet. 1999;82(1):60-66.

Battaglia A. On the selection of patients with developmental delay/mental retardation and autism spectrum disorders for genetic studies. Am J Med Genet A. 2007;143(8):789-790.

Curry CJ, Stevenson RE, Aughton D, Byrne J, Carey JC, Cassidy S, Cunniff C, Graham JM Jr, Jones MC, Kaback MM, Moeschler J, Schaefer GB, Schwartz S, Tarleton J, Opitz J. Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics. Am J Med Genet. 1997;72(4):468-477.

Dave BJ, Sanger WG. Role of cytogenetics and molecular cytogenetics in the diagnosis of genetic imbalances. Semin Pediatr Neurol. 2007;14(1):2-6.

Hamilton S. Screening for developmental delay: reliable, easy-to-use tools. J Fam Pract. 2006;55(5):415-422.

Moeschler JB, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. 2006;117(6):2304-2316.

Oberklaid F, Efron D. Developmental delay--identification and management. Aust Fam Physician. 2005;34(9):739-742.

Rydz D, Shevell MI, Majnemer A, Oskoui M. Developmental screening. J Child Neurol. 2005;20(1):4-21.

Shaffer LG, Beaudet AL, Brothman AR, Hirsch B, Levy B, Martin CL, Mascarello JT, Rao KW. Microarray analysis for constitutional cytogenetic abnormalities. Genet Med. 2007;9(9):654-662.

Shaffer LG. American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation. Genet Med. 2005;7(9):650-654.

Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, Majnemer A, Noetzel M, Sheth RD. 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. 2003;60(3):367-380.

Shevell M. Office evaluation of the child with developmental delay. Semin Pediatr Neurol. 2006;13(4):256-261.

Srour M, Mazer B, Shevell MI. Analysis of clinical features predicting etiologic yield in the assessment of global developmental delay. Pediatrics. 2006;118(1):139-145.

Medical Reviewers

Bayrak-Toydemir, Pinar , M.D., Ph.D. Assistant Medical Director, Molecular Genetics at ARUP Laboratories; Assistant Professor (Clinical), Pathology, University of Utah

Lamb, Allen N., Ph.D. Medical Director, Cytogenetics, ARUP Laboratories; Associate Professor, Department of Pathology, University of Utah

Lyon, Elaine, Ph.D. Medical Director, Molecular Genetics at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Mao, Rong , M.D. Co-Medical Director, Molecular Genetics at ARUP Laboratories; Assistant Professor, Pathology, University of Utah

Rope, Alan F., M.D. Assistant Professor of Pediatrics, Division of Medical Genetics, University of Utah

South, Sarah T. , Ph.D. Medical Director, Cytogenetics at ARUP Laboratories; Assistant Medical Director, CGH Microarray Laboratory, and Assistant Professor, Department of Pediatrics, University of Utah

Comprehensive Review: September 2008
Last Update: September 2008