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Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 2 via the AKT3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
13343 AKT3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13343AKT381479 81479,81479 $890 Order Options and Pricing

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

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-2 is a rare, early onset neurological disorder. The major symptoms include enlarged head circumference or macrocephaly, megalencephaly, ventriculomegaly, hydrocephalus, cortical malformations, heterotopia, polymicrogyria, severe intellectual disability, seizures, and postaxial polydactyly in hands and feet. Patients also present other minor symptoms such as a mild connective tissue dysplasia, skin hyperextensibility and vascular malformations. Brain MRI reveals megalencephaly, ventriculomegaly and other brain malformations (Rivière et al. 2012. PubMed ID: 22729224; Nellist et al. 2015. PubMed ID: 25523067; Negishi et al. 2017. PubMed ID: 28086757; Nakamura et al. 2014. PubMed ID: 23745724; Alcantara et al. 2017. PubMed ID: 28969385).  

As megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome can be caused by defects in a number of genes (AKT3, CCND2, and PIK3R2) with variable and overlapping presentations, they can be difficult to diagnose by clinical manifestation and image studies only. An accurate molecular diagnosis is critical for treatment, prognosis, as well as future family planning.

Genetics

AKT3-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-2 is inherited in autosomal dominant mannerPathogenic variants in AKT3 include missense, large deletions and duplications (Human Gene Mutation Database). Almost all cases carry a de novo variant (Alcantara et al. 2017. PubMed ID: 28969385; Rivière et al. 2012. PubMed ID: 22729224). Somatic mosaicism has been associated with hemimegalencephaly (Alcantara et al. 2017. PubMed ID: 28969385). AKT3 is relatively intolerant to both missense and loss-of-function variants (Genome Aggregation Database).

AKT3 encodes AKT serine/threonine kinase 3, a member of the AKT protein family which is one of the core components of the phosphatidylinositol-3-kinase (PI3K)-AKT- -mTOR pathway in vascular, limb and brain development (Rivière et al. 2012. PubMed ID: 22729224; Negishi et al. 2017. PubMed ID: 28086757). Functional analysis of the pathogenic variants in AKT3 showed a significant increase of catalytic kinase activity. This is consistent with a mechanism that the elevated PI3K-AKT-MTOR signaling results in brain overgrowth disorders (Alcantara. 2017. PubMed ID: 28969385). This is also supported by a knock out mouse model of Akt3-/- which presented a selective 20% decrease in brain size (Easton et al. 2005. PubMed ID: 15713641). AKT3-related disorder is a relatively rare cause of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (Rivière et al. 2012. PubMed ID: 22729224; Alcantara et al. 2017. PubMed ID: 28969385).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity of AKT3 in a large cohort of patients with AKT3-related phenotypes is unavailable in the literature because most studies are case reports. However, pathogenic variants in this gene are a rare cause of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Analytical sensitivity should be high.

Testing Strategy

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

This test provides full coverage of all coding exons of the AKT3 gene 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 full 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

The test is recommended for patients suspected to have AKT3-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-2. Targeted testing is indicated for family members of patients who have a known pathogenic variant in AKT3.

Gene

Official Gene Symbol OMIM ID
AKT3 611223
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Alcantara et al. 2017. PubMed ID: 28969385
  • Easton et al. 2005. PubMed ID: 15713641
  • Genome Aggregation Database (gnomAD).
  • Human Gene Mutation Database (Biobase).
  • Nakamura et al. 2014. PubMed ID: 23745724
  • Negishi et al. 2017. PubMed ID: 28086757
  • Nellist et al. 2015. PubMed ID: 25523067
  • Rivière et al. 2012. PubMed ID: 22729224

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

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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: $
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