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  • Test code: 03404
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Rett and Angelman Syndromes and Related Disorders Panel

Test description

The Invitae Rett and Angelman Syndromes and Related Disorders Panel analyzes genes that are associated with early-onset developmental disorders related to the Rett/Angelman spectrum. These syndromic disorders present with seizures, developmental delay, speech and language delays, intellectual disability, and variable congenital anomalies; some include characteristic dysmorphic features. These genes were curated based on the available evidence to date in order to provide analysis for the Rett/Angelman spectrum and related disorders. Some genes in this test may also be associated with additional unrelated disorders, which are not included in the list of disorders tested. Genetic testing of these genes may help confirm a clinical diagnosis, help predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.

This assay includes sequencing and deletion/duplication analysis of UBE3A but does not detect uniparental disomy or imprinting center defects.

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Primary panel (40 genes)

ADSL ALDH5A1 ARX ATRX CAMK2B CDKL5 CLTC CNTNAP2 CTNNB1 DDX3X DYRK1A EHMT1 FOLR1 FOXG1 GABBR2 GRIA3 GRIN2A GRIN2B HDAC8 IQSEC2 KANSL1 KCNA2 MBD5 MECP2 MEF2C NGLY1 NRXN1 SATB2 SCN2A SCN8A SLC6A1 SLC9A6 SMC1A STXBP1 SYNGAP1 TBL1XR1 TCF4 UBE3A WDR45 ZEB2

Alternative tests to consider

Broad disorders tested

  • Adenylosuccinate lyase (ADSL) deficiency
  • Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome
  • Angelman syndrome
  • Beta-propeller protein-associated neurodegeneration (BPAN)
  • Cerebral folate deficiency
  • Cornelia de Lange syndrome
  • Developmental and epileptic encephalopathy (DEE)
  • Glass syndrome
  • Kleefstra syndrome
  • Koolen-de Vries syndrome
  • Mowat-Wilson syndrome
  • Myclonic-atonic epilepsy
  • NGLY1-congenital disorder of glycosylation (CDG-Iv)
  • Pierpont syndrome
  • Pitt-Hopkins syndrome
  • Rett syndrome, atypical Rett syndrome
  • Succinic semialdehyde dehydrogenase (SSADH) deficiency

Individual disorders tested

  • adenylosuccinate lyase (ADSL) deficiency
  • alpha-thalassemia X-linked intellectual disability (ATRX) syndrome
  • Angelman syndrome, Angelman-like syndrome, Christianson syndrome
  • ARX-related conditions (developmental and epileptic encephalopathy, West syndrome, lissencephaly with ambiguous genitalia)
  • atypical Rett syndrome
  • CDKL5-related conditions (Angelman-like syndrome, atypical Rett syndrome, developmental and epileptic encephalopathy, West syndrome)
  • cerebral folate deficiency
  • CNTNAP2-related conditions (cortical dysplasia-focal epilepsy syndrome, Pitt-Hopkins-like syndrome)
  • Cornelia de Lange syndrome (CdLS)
  • developmental and epileptic encephalopathy (DEE), early infantile epileptic encephalopathy (EIEE), West syndrome
  • GABBR2-related conditions (developmental and epileptic encephalopathy, congenital Rett syndrome)
  • Glass syndrome
  • intellectual disability
  • Kleefstra syndrome
  • Koolen-de Vries syndrome
  • MECP2 duplication syndrome
  • Mowat-Wilson syndrome
  • myoclonic-atonic epilepsy (MAE), Doose syndrome
  • NGLY1-congenital disorder of glycosylation (CDG-Iv)
  • Pierpont syndrome
  • Pitt-Hopkins syndrome, Pitt-Hopkins-like syndrome
  • Rett syndrome, atypical Rett syndrome, congenital Rett syndrome
  • succinic semialdehyde dehydrogenase (SSADH) deficiency
  • WDR45-related conditions (beta-propeller protein-associated neurodegeneration, developmental and epileptic encephalopathy, Rett syndrome)

To view the complete clinical description of this panel, click here.

Rett and Angelman syndromes and related disorders can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ADSL NM_000026.2
ALDH5A1 NM_001080.3
ARX* NM_139058.2
ATRX NM_000489.4
CAMK2B NM_001220.4
CDKL5 NM_003159.2
CLTC NM_001288653.1
CNTNAP2 NM_014141.5
CTNNB1 NM_001904.3
DDX3X* NM_001193416.2
DYRK1A NM_001396.3
EHMT1 NM_024757.4
FOLR1 NM_016725.2
FOXG1 NM_005249.4
GABBR2 NM_005458.7
GRIA3 NM_000828.4
GRIN2A NM_000833.4
GRIN2B NM_000834.3
HDAC8 NM_018486.2
IQSEC2 NM_001111125.2
KANSL1* NM_001193466.1
KCNA2 NM_004974.3
MBD5 NM_018328.4
MECP2 NM_004992.3; NM_001110792.1
MEF2C NM_002397.4
NGLY1 NM_018297.3
NRXN1 NM_001135659.1
SATB2 NM_015265.3
SCN2A NM_021007.2
SCN8A* NM_014191.3; NM_001330260.1
SLC6A1 NM_003042.3
SLC9A6 NM_006359.2
SMC1A NM_006306.3
STXBP1 NM_003165.3
SYNGAP1 NM_006772.2
TBL1XR1 NM_024665.4
TCF4 NM_001083962.1
UBE3A* NM_130838.1
WDR45 NM_007075.3
ZEB2 NM_014795.3

ARX: Analysis is validated to detect polyalanine expansions but sensitivity may be reduced.
DDX3X: Sequencing analysis is not offered for exon 3.
KANSL1: Deletion/duplication analysis is not offered for exons 2-3.
SCN8A: Analysis includes exon 6 of NM_001330260.1.
UBE3A: Analysis includes sequencing and deletion/duplication analysis but does not detect uniparental disomy or imprinting center defects.