Submission Details

Submitter:

Classification:
Definitive
GENCC:100001
Gene:
Disease:
generalized epilepsy with febrile seizures plus
Mode Of Inheritance:
Autosomal dominant
Evaluated Date:
09/06/2019
Evidence/Notes:

Generalized epilepsy with febrile seizures plus (GEFS+) is a rare autosomal dominant, familial condition with incomplete penetrance and variable expressivity. It includes a spectrum from commonly mild (such as febrile seizure alone) to rarely severe (including medically treatable generalized epilepsy, intractable generalized epilepsy, or in some cases Dravet syndrome) epilepsy. Individuals with GEFS+ often have febrile seizures (or FS+) in early childhood, followed by occasional tonic, clonic, myoclonic, or absence seizures that respond to medication and remit by late childhood or early adolescence. Intermediate phenotypes with myoclonic, absence, or focal epilepsy are also included. More than 95% of individuals with GEFS+ have a parent with the same SCN1A pathogenic variant (Gennaro et al, 2003); however, the risk of developing seizures is less than 100% because of reduced penetrance, estimated to be 70% for the GEFS+ phenotype (Bonanniet al, 2004). In summary, SCN1A is definitively associated with Generalized Epilepsy with Febrile Seizures Plus. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.

PubMed IDs:
10742094 11254444 11254445 11524484 11756608 12086636 12576172 14702334 17537961 19409490 24257433 25378155 25576396 28084635 28842445
Public Report:
Assertion Criteria:
Submitter Submitted Date:
12/05/2025

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