Early Infantile Epileptic Encephalopathy or Kohlschütter-Tönz Syndrome via the SLC13A5 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT
8283 SLC13A5$640 8147981479,81479 Add to Order

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

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

Turnaround Time

18 days on average

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Early infantile epileptic encephalopathy 25 is characterized by neonatal seizures as early as the first hours and first week of life. Symptoms include focal chronic seizures, hemiconvulsions and generalized tonic-clonic seizures. Almost all patients have severe developmental delay and absence of speech. Other clinical manifestations include mild to severe intellectual disability, tooth dysplasia, plus variable combinations of ataxia, axial hypotonia, peripheral hypertonia, choreoathetosis, spasticity, and microcephaly. The frequency and severity of seizures tend to improve with age. A few patients can be even seizure-free between 3 and 7 years of age. EEG studies show mostly focal abnormalities. Experiments with a ketogenic diet have produced conflicting results (Thevenon et al. 2014; Hardies et al. 2015; Klotz et al. 2016). Some antiepileptic drugs targeting the γ-aminobutyric acid system may reduce seizure frequency (Klotz et al. 2016).

SLC13A5-related Kohlschütter-Tönz syndrome is characterized by neonatal epileptic encephalopathy and hypoplastic amelogenesis imperfecta (Schossig et al. 2016).

Genetics

Early infantile epileptic encephalopathy 25 is inherited in an autosomal recessive manner and is caused by pathogenic variants in SLC13A5 encoding solute carrier family 13, member 5, which is a sodium/citrate cotransporter. Pathogenic variants in SLC13A5 include missense, nonsense, small deletion/insertion and splice pathogenic variants. No large deletions/duplications in the SLC13A5 locus have been reported (Thevenon et a.l 2014; Hardies et al. 2015; Klotz et al. 2016; Human Gene Mutation Database). Pathogenic variants produce inactive sodium/citrate transporter due to affected helix packing and substrate binding (Klotz et al. 2016). However, the mechanisms by which pathogenic variants in SLC13A5 cause epilepsy are not understood (Klotz et al. 2016).

Kohlschütter-Tönz syndrome is also inherited in an autosomal-recessive manner and is frequently caused by biallelic pathogenic variants in ROGDI. Recently, SLC13A5 was discovered as the second major gene associated with Kohlschütter-Tönz syndrome (Schossig et al. 2016).

Testing Strategy

This test provides full coverage of all coding exons of the SLC13A5 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing and CNV

Clinical sensitivity of SLC13A5 testing in a large cohort of patients with early infantile epileptic encephalopathy is unavailable in the literature, because only a limited number of cases have been reported. For Kohlschütter-Tönz syndrome, SLC13A5 pathogenic variants were identified in all 10 patients with ROGDI-negative Kohlschütter-Tönz syndrome (Schossig et al. 2016). All reported SLC13A5 pathogenic variants are detectable by sequencing.

Indications for Test

SLC13A5 sequencing is recommended for patients who are suspected to have early infantile epileptic encephalopathy 25 or ROGDI-negative Kohlschütter-Tönz syndrome. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC13A5.

Gene

Official Gene Symbol OMIM ID
SLC13A5 608305
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Epileptic Encephalopathy, Early Infantile, 25 AR 615905

Related Test

Name
Epilepsy and Seizure Plus Panel

Citations

  • Hardies K. et al. 2015. Brain. 138: 3238-50. PubMed ID: 26384929
  • Human Gene Mutation Database (Bio-base).
  • Klotz J. et al. 2016. Molecular Medicine. 22: 310-321. PubMed ID: 27261973
  • Schossig A. et al. 2016. Journal of Medical Genetics. PubMed ID: 27600704
  • Thevenon J. et al. 2014. American Journal of Human Genetics. 95: 113-20. PubMed ID: 24995870

Ordering/Specimens

Ordering Options

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.

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

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