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Cortical Dysplasia-Focal Epilepsy Syndrome via the CNTNAP2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
CNTNAP2 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4581CNTNAP281406 81406,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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

Cortical dysplasia-focal epilepsy syndrome (CDFE) or Pitt-Hopkins like syndrome 1 (PTHSL1; OMIM:610042) is a neurodevelopmental disorder characterized by intractable seizures and severe intellectual disability. Patients show normal development prior to seizure onset at 14-20 months (Strauss et al. N Engl J Med 354(13):1370-1377, 2006). Following seizure onset, there is mental regression as well as deterioration of social behavior and language skills reminiscent of Autism Spectrum Disorders (ASD) (Zweier et al. Am J Hu Gen 85(5):655-666, 2009). CDFE patients suffer from frequent focal seizures throughout childhood and seizures often become intractable with age. Variable features of CDFE include hyperactivity, hyperbreathing and neonatal hypotonia (Zweier et al., 2009).


CDFE is inherited in an autosomal recessive manner and is caused by loss-of-function mutations in the CNTNAP2 gene. The c.3709delG mutation has been identified as a founder mutation in Old Order Amish families (Strauss et al., 2006; Jackman et al. Pediatr Neurol 40(4):310-313, 2009). Heterozygous variants in CNTNAP2 have been associated with some cases of Autism Spectrum Disorder (ASD), however no direct causative link has been demonstrated (Bakkaloglu et al. Am J Hu Genet 82(1):165-173, 2008).

CNTNAP2 encodes the protein CASPR2. CASPR2 is a neuronally expressed transmembrane protein. CASPR2 is important for mediating axo-glial interactions as well as for the proper clustering of K+ channels in juxtaparanodal regions along myelinated axons (Poliak et al. J Cell Biol.162(6):1149-1160, 2003). CNTNAP2 knockout mice phenocopy CDFE patients and have defects in neuronal migration, suggesting a possible etiology (Penagarikano et al. Cell 147(1):235-246, 2011).

While a variety of mutation types have been reported in CNTNAP2, approximately 50% of the reported disease causing variants are point mutations or small deletions and approximately 50% are large deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

Approximately 50% of the reported disease causing variants in CNTNAP2 are point mutations or small deletions that would be detectable via sequencing (Zweier et al. Am J Hu Genet 85(5):655-666, 2009; Strauss et al. N Engl J Med 354(13):1370-1377, 2006). CNTNAP2 mutations were found in <1% of patients diagnosed with Pitt-Hopkins syndrome, but who lacked a TCF4 mutation (Zweier et al., 2009).

Approximately 50% of the reported disease causing variants in CNTNAP2 are large deletions (Zweier et al., 2009; Strauss et al., 2006).

Testing Strategy

This test provides full coverage of all coding exons of the CNTNAP2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for CNTNAP2 testing include patients with symptoms of CDFE with a family history consistent with autosomal recessive inheritance. Individuals diagnosed with Pitt-Hopkins syndrome, but for which no TCF4 mutation was identified are also candidates for CNTNAP2 sequencing (Zweier et al., 2009). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CNTNAP2.


Official Gene Symbol OMIM ID
CNTNAP2 604569
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Cortical Dysplasia-Focal Epilepsy Syndrome AR 610042


  • Bakkaloglu, B. et al. (2008). "Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Dsiorders." Am J Hu Genet 82(1):165-173. PubMed ID: 18179895
  • Human Gene Mutation Database (Bio-base).
  • Jackman, C. et al. (2009). "Gene Associated with Seizures, Autism, and Hepatomegaly in an Amish Girl." Pediatr Neurol 40(4):310-313. PubMed ID: 19302947
  • Penagarikano, O. et al. (2011). "Absence of CNTNAP2 Leads to Epilepsy, Neuronal Migration Abnormalities, and Core Autism-Related Deficits." Cell 147(1):235-246. PubMed ID: 21962519
  • Poliak, S. et al. (2003). "Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1." J Cell Biol 162(6):1149-1160. PubMed ID: 12963709
  • Strauss, K.A. et al. (2006). "Recessive Symptomatic Focal Epilepsy and Mutant Contactin-Associated Protein-like 2." N Engl J Med 354(13):1370-1377. PubMed ID: 16571880
  • Zweier, C. et al. (2009). "CNTNAP2 and NRXN1 Are Mutated in Autosomal-Recessive Pitt-Hopkins-like Mental Retardation and Determine the Level of a Common Synaptic Protein in Drosophila." Am J Hu Genet 85(5):655-666. PubMed ID: 19896112


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

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