epilepsy genes
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Get to know the genes behind epilepsy

We’ve previously looked at examples of the spectrum of genetic seizure disorders: ranging from syndromes where seizures are the only symptoms (for example, GEFS+ and Dravet syndrome) to disorders that manifest with seizures along with additional features such as intellectual disability (for example, Fragile X syndrome and Rett syndrome).

We’ve also discussed how phenotypic overlap between different syndromes can complicate diagnosing a seizure disorder. And how a variety of inheritance patterns (including autosomal dominant, autosomal recessive, X-linked, de novo and mitochondrial mechanisms) across hundreds of potentially relevant genes further complicate matters.

Today we’re taking a look at some important epilepsy genes for which testing can be particularly tricky due to their propensity for deletion and/or duplication variants. It is for cases like these, among others, that a multigene panel which includes deletion/duplication analysis is most often the recommended testing approach for patients presenting with symptoms of a genetic seizure disorder. And it is why the selection of a test like Genomic Unity® Epilepsy Analysis with full del/dup coverage of the epilepsy genes being tested is so important.

SCN1A1

SCN1A seizure disorders

InheritanceAutosomal dominant
Proportion of causal del/dup variants>25%
Clinical symptoms include
  • Dravet syndrome
  • Febrile seizures
  • Febrile seizures plus (FS+)
  • Generalized epilepsy involving tonic, clonic, tonic-clonic, myoclonic or absence seizures
  • Generalized epilepsy with febrile seizures plus (GEFS+)
  • Infantile partial seizures with variable foci
  • Intractable childhood epilepsy with generalized tonic-clonic seizures
  • Severe myoclonic epilepsy, borderline (SMEB)

KCNQ22

KCNQ2-related benign familial neonatal epilepsy (KCNQ2-BFNE), KCNQ2-related neonatal epileptic encephalopathy (KCNQ2-NEE)

InheritanceAutosomal dominant
Proportion of causal del/dup variantsUp to 40%
Clinical symptoms include
  • Associated focal motor and autonomic features
  • Focal clonic activity
  • Neonatal epilepsy
  • Neonatal epileptic encephalopathy
  • Tonic or apneic episodes

  • Developmental impairment

STXBP13

Early-Infantile Epileptic Encephalopathy 4

InheritanceAutosomal dominant
Proportion of causal del/dup variants~17%
Clinical symptoms include
  • Generalized tonic-clonic, clonic, or tonic seizures
  • Infantile spasms
  • Myoclonic, focal, atonic, and absence seizures

  • Movement disorders (ataxia, dystonia)
  • Behavior disorders (autism)
  • Developmental impairment

EPM2A4, NHLRC14

Progressive Myoclonus Epilepsy, Lafora Type

InheritanceAutosomal recessive
Proportion of causal del/dup variants10-15%, <10%
Clinical symptoms include
  • Focal occipital seizures
  • Fragmentary, symmetric, or generalized myoclonus
  • Generalized seizures including tonic-clonic seizures, absence seizures or drop attacks

  • Movement disorders (ataxia, spasticity, dysarthria)
  • Behavioral deterioration
  • Cognitive impairment

Going one step further, Genomic Unity® Epilepsy Analysis additionally includes tandem repeat expansion analysis of the CSTB epilepsy gene which is causal for progressive myoclonic epilepsy type I as well as repeat expansion analysis of 4 loci which are causal for intellectual disability disorders that often present with seizures as a symptom: AFF2, AFF3, DIB2B, FMR1.

CSTB5

Progressive Myoclonic Epilepsy Type 1

InheritanceAutosomal recessive
Proportion of causal repeat expansions>90%
Clinical symptoms include
  • Stimulus-sensitive myoclonus seizures
  • Tonic-clonic epileptic seizures

  • Movement disorders (ataxia, dysarthria)

The longer a patient has uncontrolled seizures, the greater the likelihood that they will suffer irreparable brain damage. The ability to quickly arrive at a genetic cause of epilepsy through a comprehensive testing method such as Genomic Unity® Epilepsy Analysis can provide the information needed to control an individual’s seizures as soon as possible, allowing for better clinical management, prognosis and overall quality of life.

References

  1. SCN1A Seizure Disorders https://www.ncbi.nlm.nih.gov/books/NBK1318/
  2. KCNQ2-Related Disorders https://www.ncbi.nlm.nih.gov/books/NBK32534/
  3. STXBP1 Encephalopathy with Epilepsy https://www.ncbi.nlm.nih.gov/books/NBK396561/
  4. Progressive Myoclonus Epilepsy, Lafora Type https://www.ncbi.nlm.nih.gov/books/NBK1389/
  5. Progressive Myoclonic Epilepsy Type I https://www.ncbi.nlm.nih.gov/books/NBK1142/

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