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What Does SLC13A5 Epilepsy Look Like? (Clinical Symptoms)
The following symptoms are commonly associated with SLC13A5 Epilepsy. If your loved one has a majority of these clinical features, genetic testing may be recommended by your physician.
Seizures
- Seizures beginning within the first few days of life
- Seizures are often most difficult to control early in life and most loved ones remain on seizure medication into adulthood
- Multiple types of seizures, including focal (neonatal focal seizure), tonic clonic, and myoclonic seizures
- Seizures can be severe, lasting from minutes to hours and sometimes requiring rescue medications and hospitalizations
- Seizures are often difficult to control with anti-seizure medications (refractory seizures)
- Some loved ones can achieve seizure control with a combination of anti-seizure medications
Movement Disorder
- Low muscle tone (hypotonia). Infants and young children experiencing this symptom are often described as “floppy.” You may notice a loved one feeling limp when you hold them and showing less control of their neck muscles, causing their head to drop. It may also be difficult for them to place weight on their leg or shoulder muscles.
- Lack of muscle control and/or coordination of voluntary movements, such as walking or picking up an object (ataxia)
- Episodes of body stiffening or weakness lasting a few minutes to a few hours
- Excessive drooling
Developmental Delay
- Severe difficulty with speech production (expressive language delay), with better ability to understand language (receptive language)
- Motor delay
- Cognitive delay
Other Characteristics
- Poor development of teeth (hypodontia) or weakness of teeth enamel
- Brain MRI that appears normal or has subtle changes in the white matter
- EEGs have a relatively well-preserved background for age, even in the face of frequent seizures
- Elevated Citrate levels in blood and cerebrospinal fluid (CSF)
The disease phenotype (the observable characteristics of the disease) is variable so that even siblings with the same genetic mutation will show differences in the severity of symptoms, including differences in the type and the frequency of seizures and differences in their developmental milestone timeline.
How do I confirm SLC13A5 Epilepsy with genetic testing?
Several genetic tests are available to confirm SLC13A5 Epilepsy. These tests can be performed on either blood or saliva samples. Genetic tests include Whole Exome Sequencing (WES), Epilepsy Gene Panel (SLC13A5 is included in many epilepsy panels) or Targeted testing (please scroll to mid-page). Only if both the copies of the child’s SLC13A5 genes are mutated, is it considered to be disease causing. SLC13A5 Epilepsy is a recessively inherited genetic disorder.
Identify Your Genetic Team
Your testing team may include a geneticist, a genetic counselor, and a neurologist. A geneticist is a medical doctor with specialty training who will choose which genetic tests to perform, interpret the results, and explain them to your family. Genetic counselors advise families about genetic tests and help them understand the results and connect to resources and clinical research. A neurologist or epileptologist may also be able to order genetic testing for your loved one.
Find Genetic Testing
Free genetic testing for children under 8 years old is available through Behind the Seizure. Free genetic testing for people over 8 years old can be performed through TESS Research Foundation’s partnership with the Broad Institute. You can ask your physician if you meet the criteria and to help you access the free testing. You can find genetic testing locations here. TESS Research Foundation has also recently partnered with Probably Genetic to further increase access to no-cost genetic testing for pediatric epilepsy disorders within our community. You can take a short quiz to apply to Probably Genetic’s program and determine eligibility. Navigating genetic testing can be difficult. If you need help, please contact TESS Research Foundation at info@tessfoundation.org.
Interpret Genetic Test
Following testing, there are several possible results including a positive test result, a negative test result, or an uncertain test result.
- A positive result means that a genetic change has been identified as the cause of epilepsy. If you receive a positive diagnosis, visit Patients & Caregivers and join the TESS registry.
- A negative result in a person with epilepsy means that a genetic cause of epilepsy was not identified using the test performed but it does not rule out the possibility of a genetic diagnosis and additional testing may be considered. You might also visit the Undiagnosed Diseases Network (UDN) which seeks to provide answers for patients and families affected by mysterious conditions.
- Uncertain results may be referred to as genetic variants of uncertain or unknown significance (VUS). They may be re-interpreted at a later date when more information becomes available and can be re-classified as either negative or positive. If your child has a SLC13A5 variant of unknown significance, please upload your genetic report into our Registry so we can offer assistance. If you need help, please contact TESS Research Foundation at info@tessfoundation.org.
Reading a genetic report for SLC13A5
For someone to be diagnosed with SLC13A5 Epilepsy, there needs to be 2 changed copies of the SLC13A5 gene, one copy from the mom and one from the dad. The term for this is monogenic recessive, meaning a patient needs two changed copies of the SLC13A5 gene to be diagnosed with SLC13A5 Epilepsy. People with one normal copy and one changed copy of SLC13A5 are carriers. The variant of unknown or uncertain significance (VUS) means that scientists don’t know whether this SLC13A5 gene change leads to SLC13A5 Epilepsy.
If there are two different changes to SLC13A5, one on each copy of the gene, the genetic report may look like this:
- Heterozygous pathogenic and likely pathogenic variants in SLC13A5 gene detected.
- This individual is compound heterozygous for a pathogenic and a likely pathogenic variant in the SLC13A5 gene.
This indicates that the person has SLC13A5 Epilepsy.
If the changes are the same, meaning that the mom and dad each share the same change in the SLC13A5 gene, the genetic report may look like this:
- Homozygous for pathogenic mutations in SLC13A5 gene.
This indicates that the person has SLC13A5 Epilepsy.
If the changes to each copy of the SLC13A5 gene are the same, but scientists do not know whether the changes are pathogenic, the genetic report may look like this:
- Homozygous for variant of unknown significance in the SLC13A5 gene.
This indicates that the person may have SLC13A5 Epilepsy.
If there is only one copy of the gene change, the genetic report may look like this:
- The individual is heterozygous for SLC13A5 with one variant of unknown significance.
This means that the person has only one changed copy of the SLC13A5 gene and one normal copy. This person would be a carrier of SLC13A5 Epilepsy.
What About SLC13A5 Carriers
With few exceptions, all people have two copies of every gene. In many cases, the extra copy can act as a “back up” if one of the copies is defective. It appears that you need to have a change in the DNA sequence of both copies of your SLC13A5 gene in order to have a SLC13A5 Epilepsy. This means that you must inherit a copy with an abnormal sequence from both your mom and your dad (autosomal recessive inheritance). Because the mothers and fathers appear healthy when they each have just a single defective copy of the gene, it appears you only get the disease when you inherit two abnormal copies. However, if you are a carrier, this may affect your family planning decisions.
If you are a carrier of an SLC13A5 variant, you may want to consider the following:
- Have your partner tested
- Talk to a genetic counselor
- Your extended family may also be carriers. They may want to consider genetic testing and counseling.
Are you Newly Diagnosed? Visit our Patients & Caregivers Section.
Medical Disclaimer: Please note that this site should not and does not replace medical information or advice from health care professionals.