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Developmental delay (DD) is any significant lag in a child's physical, cognitive, emotional, or social maturity when compared to established norms. Intellectual disability (ID) is defined as neurocognitive impairments (IQ <70) as well as significant limitations in adaptive living skills (social, communication, work, leisure, daily living).
Tests generally appear in the order most useful for common clinical situations
| Test name: Cytogenomic SNP Microarray |
| ARUP #: 2003414 |
| Methodology: Genomic Microarray (Oligo-based array) |
| Use: First-tier test for indication of ID, DD, dysmorphic features, congenital anomalies and autism |
| Test name: Fragile X (FMR1) Screen with Reflex to Fragile X (FMR1) Diagnostic |
| ARUP #: 2001946 |
| Methodology: Polymerase Chain Reaction/Fragment Analysis |
| Use: Identify carrier status of asymptomatic females with a family history of DD/ID/ASD in individuals (usually males) with neurocognitive dysfunction/ASD, especially those with a family history suggestive of an X-linked pattern of inheritance who are planning a pregnancy/already pregnant May also be used as a cost-effective newborn screen to identify affected individuals or as a carrier screen If screen suggests a pre- or full mutation, Fragile X Diagnostic will be added for analysis of sizing and methylation |
| Limitations: Rare FMR1 mutations unrelated to trinucleotide expansion may not be detected Precise sizing of CGG repeats is not provided Intermediate alleles will not be reported Clinical sensitivity and specificity are 99% for pre- and full-mutation alleles |
| Test name: Fragile X (FMR1) Diagnostic |
| ARUP #: 0040011 |
| Methodology: Southern Blot/Polymerase Chain Reaction/Fragment Analysis |
| Use: Identify individuals (usually males) with neurocognitive dysfunction/ASD, especially those with a family history suggestive of an X-linked pattern of inheritance, or individuals with late-onset cerebellar ataxia and intention tremor of unknown etiology Identify carrier status of females experiencing primary ovarian insufficiency or fertility problems associated with elevated FSH levels and a family history of fragile X syndrome |
| Limitations: DNA analysis of the CGG repeat region is >99% sensitive and is 100% specific for diagnostic/carrier testing with the exception of a "gray zone" of 45-54 CGG repeats where carrier test results are inconclusive
Reliability of test results exceeds 99% |
| Test name: Rett Syndrome (MECP2), Full Gene Sequencing |
| ARUP #: 0051378 |
| Methodology: Polymerase Chain Reaction/Sequencing |
| Use: Confirm Rett syndrome Aid in determining etiology for DD/ID/ASD especially in females with microcephaly, seizures, delayed expressive language and a lack of birth defects |
| Limitations: Deep intronic mutations and large deletions/duplications will not be identified; analytical sensitivity may be compromised by rare primer site mutations Sequencing testing limited to females; males do not survive mutations or deletions Males are candidates for duplication analysis by multiplex ligation probe amplification Clinical sensitivity for Rett syndrome is ~80% |
| Test name: Rett Syndrome (MECP2), Full Gene Analysis |
| ARUP #: 0051614 |
| Methodology: Full Gene Sequencing/Multiplex Ligation Probe Amplification |
| Use: Confirm Rett syndrome Aid in determining etiology for DD/ID/ASD, especially in females with microcephaly, seizures, delayed expressive language and a lack of birth defects Includes Rett syndrome (MECP2) full gene sequencing as well as deletion/duplication |
| Limitations: Breakpoints of large deletions/duplications will not be determined; deep intronic mutations will not be detected; analytical sensitivity may be compromised by rare primer site mutations Clinical sensitivity for Rett syndrome is ~95% |
| Test name: Rett Syndrome (MECP2), Deletion and Duplication |
| ARUP #: 0051618 |
| Methodology: Multiplex Ligation Probe Amplification |
| Use: Confirm Rett syndrome Aid in determining etiology for DD/ID/ASD, especially in females with microcephaly, seizures, delayed expressive language and a lack of birth defects |
| Limitations: Breakpoints of large deletions/duplications will not 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 Clinical sensitivity up to 15% |
| Test name: PTEN-Related Disorders (PTEN) Sequencing and Deletion/Duplication |
| ARUP #: 2002470 |
| Methodology: Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification |
| Use: Test for Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome |
| Limitations: Rare diagnostic errors can occur due to primer or probe-site mutations Some regulatory region mutations, deep intronic mutations and large deletions of single exon 3 are not detected |
| Test name: X Chromosome Ultra-High Density Microarray, 954 Genes |
| ARUP #: 2004434 |
| Methodology: Exonic Oligonucleotide-based CGH Microarray |
| Use: Detect loss or gain of DNA on the X chromosome in patients with unexplained disability, autism, and other X-linked genetic conditions |
| Limitations: Does not detect numerical X-chromosome changes, such as Klinefelter, Turner, or triple-X syndromes Balanced rearrangements and base-pair changes will not be detected; copy-number imbalances for areas of high-sequence similarity may not be detected Negative result does not exclude diagnosis of disorders represented on the microarray |
| Test name: Angelman Syndrome and Prader-Willi Syndrome by Methylation |
| ARUP #: 2005077 |
| Methodology: Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring |
| Use: Aid in determining etiology of DD/ID in patients with additional findings associated with Angelman syndrome (AS) (microcephaly, seizures, ataxia) or PWS (feeding problems, hypotonia, hypogonadism, and growth failure in infancy; hyperphagia and rapid weight gain in early childhood) >99% clinical sensitivity |
| Limitations: Mutations or mechanisms not affecting methylation patterns will not be detected |
| Test name: Angelman Syndrome (UBE3A) Sequencing |
| ARUP #: 2005564 |
| Methodology: Polymerase Chain Reaction/Sequencing |
| Use: Confirm diagnosis of Angelman syndrome in individuals with normal DNA methylation test UBE3A sequencing identifies ~11% of individuals with Angelman syndrome |
| Test name: CDKL5-Related Disorders (CDKL5) Sequencing and Deletion/Duplication |
| ARUP #: 2004935 |
| Methodology: Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification |
| Use: Aid in determining etiology of DD/ID in female patients with additional findings associated with Rett syndrome (includes early onset intractable seizures and severe DD) |
| Limitations: Clinical sensitivity is 17% in females with infantile spasms/seizures |
| Test name: Chromosome Analysis, Peripheral Blood, with Reflex to Genomic Microarray |
| ARUP #: 2005763 |
| Methodology: Giemsa-Band Analysis and Cytogenomic Microarray SNP (Oligo-based array) |
| Use: Confirm diagnosis of a known aneuploid syndrome or detect a chromosome translocation |
| Test name: Chromosome FISH, Metaphase |
| ARUP #: 2002299 |
| 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 of screening multiple loci by FISH |
| Limitations: Detects deletions/duplications of the genome at specific, targeted loci May not detect partial imbalances of the targeted regions |
| Test name: Lead, Blood (Capillary) |
| ARUP #: 0020745 |
| Methodology: Quantitative Inductively Coupled Plasma-Mass Spectrometry |
| Use: Detect exposure to lead |
| Limitations: Elevated results may be due to skin or other collection-related contamination |
| Test name: Chromosome Analysis, Peripheral Blood |
| ARUP #: 2002289 |
| Methodology: Giemsa-Band Analysis |
| Comments: Confirm diagnosis of a known aneuploid syndrome or detect a chromosome translocation |
| Test name: Noonan Syndrome (PTPN11) Sequencing with Reflex to (SOS1) Sequencing |
| ARUP #: 2004189 |
| Methodology: Polymerase Chain Reaction/Sequencing |
| Comments: |
| Test name: Noonan Syndrome (SOS1) Sequencing |
| ARUP #: 2004195 |
| Methodology: Polymerase Chain Reaction/Sequencing |
| Comments: |
| Test name: CDKL5-Related Disorders (CDKL5) Deletion/Duplication |
| ARUP #: 2004927 |
| Methodology: Polymerase Chain Reaction/Multiplex Ligation-dependent Probe Amplification |
| Comments: Aid in determining etiology of DD/ID in female patients with additional findings associated with Rett syndrome (includes early onset intractable seizures and severe DD) |
| Test name: CDKL5-Related Disorders (CDKL5) Sequencing |
| ARUP #: 2004931 |
| Methodology: Polymerase Chain Reaction/Sequencing |
| Comments: Aid in determining etiology of DD/ID in female patients with additional findings associated with Rett syndrome (includes early onset intractable seizures and severe DD) |
| Test name: Amino Acids Quantitative, Plasma |
| ARUP #: 0080710 |
| Methodology: Ion Exchange Chromatography |
| Comments: |
| Test name: Organic Acids, Urine |
| ARUP #: 0098389 |
| Methodology: Gas Chromatography/Mass Spectrometry |
| Comments: |
| Test name: Carnitine Panel |
| ARUP #: 0081110 |
| Methodology: Tandem Mass Spectrometry |
| Comments: |