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Periventricular Heterotopia with Microcephaly via the ARFGEF2 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
ARFGEF2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11093ARFGEF281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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 platform).

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

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Periventricular heterotopia with microcephaly (PHM) is a neuronal migration disorder with onset in the first 3-9 months of life. Early symptoms include severe hypotonia, feeding problems, acquired microcephaly and infantile spasms or absence seizures (Sheen et al. 2004). Seizures occur in most patients and can be refractory to treatment. EEGs show hypsarrhythmia or other epileptiform activity (Tanyalçin et al. 2013). PHM may evolve into other seizure disorders such as West or Lennox-Gastout syndromes (Banne et al. 2013). Another characteristic of PHM is severe developmental delay and/or developmental regression. PHM patients have profound intellectual disability with absence of speech and many cannot sit or stand unassisted. MRI in PHM patients reveals diffuse periventricular heterotopia, thin corpus callosum, and cortical and hippocampal atrophy (Sheen et al. 2004; Tanyalçin et al. 2013).


PHM can be caused by variants in the ARFGEF2 gene and is inherited in an autosomal recessive manner. Missense, splice site and frameshift variants in ARFGEF2 have been reported to be pathogenic (Sheen et al. 2004; de Wit et al. 2009; Banne et al. 2013). ARFGEF2 encodes the protein BIG2. ARFGEF proteins are guanine nucleotide exchange factors (GEF) which activate ADP-ribosylation factors (ARF) (de Wit et al. 2009). ARFs regulate vesicle and membrane trafficking from the trans-Golgi network. BIG2 is one of three ARFGEF proteins expressed in the brain during neuronal development and is enriched in the cortical ventricular zone. Periventricular heterotopia is caused by the abnormal positioning of post-mitotic neurons, which occurs as a result of defects in neuronal migration. The loss of BIG2 leads to endosome recycling defects and failure to deliver proteins to the cell membrane (de Wit et al. 2009). It is hypothesized that lack of receptors for signaling molecules, such as GABAA, in the brain in the absence of BIG2 underlie the neuronal migration defects seen in PHM patients (Sheen et al. 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

No large scale sequencing of ARFGEF2 in PHM patients has been performed, thus the clinical sensitivity of ARFGEF2 sequencing in PHM is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the ARFGEF2 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

ARFGEF2 testing should be considered in patients with MRI evidence of periventricular heterotopia for which mutations in FLNA were not identified. ARFGEF2 sequencing might also be considered in unexplained cases of West syndrome (Banne et al. 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ARFGEF2.


Official Gene Symbol OMIM ID
ARFGEF2 605371
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Heterotopia, Periventricular, Autosomal Recessive AR 608097


  • Banne E, Atawneh O, Henneke M, Brockmann K, Gartner J, Elpeleg O, Edvardson S. 2013. West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation. Journal of Medical Genetics 50: 772–775. PubMed ID: 23812912
  • de Wit MCY, Coo IFM de, Halley DJJ, Lequin MH, Mancini GMS. 2009. Movement disorder and neuronal migration disorder due to ARFGEF2 mutation. neurogenetics 10: 333–336. PubMed ID: 19384555
  • Sheen VL, Ganesh VS, Topcu M, Sebire G, Bodell A, Hill RS, Grant PE, Shugart YY, Imitola J, Khoury SJ, Guerrini R, Walsh CA. 2004. Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nature Genetics 36: 69–76. PubMed ID: 14647276
  • Tanyalçin I, Verhelst H, Halley DJJ, Vanderhasselt T, Villard L, Goizet C, Lissens W, Mancini GM, Jansen AC. 2013. Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: Case study and literature review. European Journal of Paediatric Neurology 17: 666–670. PubMed ID: 23755938


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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