Rett Syndrome, Angelman Syndrome and Variant Syndromes Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3257 ARX 81404,81403 Order Options and Pricing
CAMK2B 81479,81479
CDKL5 81406,81405
CNTNAP2 81406,81479
FOXG1 81404,81479
GABRA1 81479,81479
GRIN2B 81479,81479
HDAC8 81479,81479
IQSEC2 81479,81479
KCNQ2 81406,81479
KIF1A 81479,81479
MBD5 81479,81479
MECP2 81302,81304
MEF2C 81479,81479
NRXN1 81479,81479
PDHA1 81406,81405
PPT1 81479,81479
SCN2A 81479,81479
SCN8A 81479,81479
SLC9A6 81406,81479
STXBP1 81406,81479
TCF4 81406,81405
UBE3A 81406,81479
WDR45 81479,81479
ZEB2 81405,81404
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3257Genes x (25)81479 81302(x1), 81304(x1), 81403(x1), 81404(x3), 81405(x4), 81406(x8), 81479(x32) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Rett syndrome is a neurodevelopmental disorder that is one of the most frequent causes of intellectual disability in females. Rett syndrome patients display normal development during early infancy, but between 6 and 18 months undergo psychomotor regression in which they lose previously acquired skills (Neul et al. 2010. PubMed ID: 21154482; Ehrhart et al. 2016. PubMed ID: 27884167). Other key features of Rett syndrome include loss of language/communication dysfunction, microcephaly, stereotyped hand-wringing motions and seizures. Variations of classic Rett syndrome, termed atypical Rett syndrome or Rett-like syndromes, have been described. Atypical Rett syndrome patients share major clinical features with classic Rett syndrome, but have variable secondary features such as bruxism, impaired sleep, and growth retardation (Neul et al. 2010. PubMed ID: 21154482; Marangi and Zollino. 2015. PubMed ID: 27617128; Vidal et al. 2019. PubMed ID: 31105003; Iwama et al. 2019. PubMed ID: 30842224). The vast majority of patients with Rett syndrome are female. Male patients with pathogenic variants in MECP2 have been reported with non-syndromic intellectual disability, absence of speech, neurodevelopmental delay, and epilepsy (Campos et al. 2007. PubMed ID: 17084570; Schönewolf-Greulich et al. 2016. PubMed ID: 26936630).

Angelman syndrome is a neurodevelopmental disorder characterized by severe intellectual disability, seizure, developmental delay, absent or minimal speech development, ataxic gait and/or tremulousness of the limbs, microcephaly and a unique behavioral phenotype that includes happy demeanor and excessive laughter. Developmental delays are first noted at 3 to 6 months age, but the unique clinical features of the syndrome do not manifest until after age 1 year (Williams et al. 2010. PubMed ID: 20445456; Dagli et al. 2012. PubMed ID: 22670133; Sato. 2017. PubMed ID: 28326016).

Genetics

This panel covers genes for Rett syndrome, Angleman syndrome and their variant syndromes which share common clinical features (Marangi and Zollino. 2015. PubMed ID: 27617128; Ehrhart et al. 2016. PubMed ID: 27884167; Vidal et al. 2019. PubMed ID: 31105003; Iwama et al. 2019. PubMed ID: 30842224). Genes in this panel are discussed briefly below:

MECP2: For Rett syndrome, the causative gene is MECP2. The syndrome is inherited in X-linked dominant manner.

Other genes in which pathogenic variants cause a similar phenotype to Rett syndrome include: CDKL5, HDAC8, IQSEC2, PDHA1 and WDR45 (X-linked dominant); ARX (X-linked recessive); FOXG1, CAMK2B, GABRA1, GRIN2B, KCNQ2, KIF1A, MEF2C, SCN2A, SCN8A and STXBP1 (autosomal dominant); PPT1 (autosomal recessive).

UBE3A: Angelman syndrome is caused by a deficiency of the imprinted and maternally expressed UBE3A gene. This means only UBE3A pathogenic variants present on the maternal allele cause Angelman syndrome. The molecular mechanisms include: (1) Deletions of the 15q11.2-q13 region, containing UBE3A (65%–70% of cases). (2) Paternal uniparental disomy of chromosome 15 (3%–7% of cases). (3) Imprinting center defects within the 15q11.2-q13 region (2%–5% of cases). (4) Loss of function pathogenic variants in the maternal UBE3A allele (5-10% of cases) (Williams et al. 2010. PubMed ID: 20445456; Dagli et al. 2012. PubMed ID: 22670133; Sadikovic et al. 2014. PubMed ID: 25212744).

Other genes for a differential diagnosis for Angelman syndrome include: SLC9A6 (X-linked recessive); TCF4, MBD5, ZEB2 (autosomal dominant); CNTNAP2 and NRXN1 (autosomal recessive).

See individual gene test descriptions for information on molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Causative point variants in MECP2 are found in 80% of typical Rett syndrome cases and 40% of atypical Rett syndrome cases (Christodoulou and Ho. 2012. PubMed ID: 20301670).

Approximately 10% of Angelman syndrome patients have pathogenic variants in the UBE3A gene (Sadikovic et al. 2014. PubMed ID: 25212744). This panel should be considered for Angelman syndrome patients that have normal methylation analysis of the 15q11.2-q13 region. Methylation analysis is the preferred first test for Angelman syndrome isolated cases. In particular, this panel does not detect imprinting defects, uniparental disomy, certain copy number variants or complex rearrangements involving chromosome 15q11.2-q13 for Angleman.

This panel has genes causative for Rett syndrome, Angelman syndrome and their variant syndromes, therefore, we predict that this panel will have a high sensitivity for identifying a causative gene in these syndromes.

Large deletions or duplications have been reported in ARX, CDKL5, CNTNAP2, FOXG1, GABRA1, GRIN2B, HDAC8, IQSEC2, KCNQ2, KIF1A, MEF2C, NRXN1, PDHA1, PPT1, SCN2A, SCN8A, STXBP1, UBE3A, WDR45, and ZEB2 (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.4% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this panel include patients with symptoms suspected for Rett syndrome, Angleman syndrome and their variant syndromes which share common clinical features.

Genes

Official Gene Symbol OMIM ID
ARX 300382
CAMK2B 607707
CDKL5 300203
CNTNAP2 604569
FOXG1 164874
GABRA1 137160
GRIN2B 138252
HDAC8 300269
IQSEC2 300522
KCNQ2 602235
KIF1A 601255
MBD5 611472
MECP2 300005
MEF2C 600662
NRXN1 600565
PDHA1 300502
PPT1 600722
SCN2A 182390
SCN8A 600702
SLC9A6 300231
STXBP1 602926
TCF4 602272
UBE3A 601623
WDR45 300526
ZEB2 605802
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Campos et al. 2007. PubMed ID: 17084570
  • Christodoulou and Ho. 2012. PubMed ID: 20301670
  • Dagli et al. 2012. PubMed ID: 22670133
  • Ehrhart et al. 2016. PubMed ID: 27884167
  • Human Gene Mutation Database (Bio-base).
  • Iwama et al. 2019. PubMed ID: 30842224
  • Marangi and Zollino. 2015. PubMed ID: 27617128
  • Neul et al. 2010. PubMed ID: 21154482
  • Sadikovic et al. 2014. PubMed ID: 25212744
  • Sato. 2017. PubMed ID: 28326016
  • Sch├Ânewolf-Greulich et al. 2016. PubMed ID: 26936630
  • Vidal et al. 2019. PubMed ID: 31105003
  • Williams et al. 2010. PubMed ID: 20445456

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×