Genetic Epilepsy with Febrile Seizures Plus (GEFS+) is an epilepsy syndrome that is seen in families.

A
GEFS+ family is defined as a family with at least 2 or more individuals with seizures seen in GEFS+, with
at least one family member with febrile seizures or febrile seizures plus.

Febrile seizures or febrile seizures plus (FS+) are the most common seizure type in GEFS+.

FS+ diagnosis means that the person has seizures (both febrile and not febrile) beyond age 6 years,
and although seizures typically stop by adolescence, they could rarely continue into adulthood.

Persons with GEFS+ usually are developmentally normal, without learning problems or intellectual
disability.

Less commonly, other seizure types like absence, myoclonic, atonic seizures, or even focal seizures
can also be seen.

Very infrequently GEFS+ families will have individuals who have a severe forms of epilepsy and
developmental delay (also called developmental and epileptic encephalopathy) like Dravet syndrome or
myoclonic atonic epilepsy (of Doose).

Several different genes have been associated with GEFS+ like SCN1A, SCN1B, GABRG2, STX1B, SCN9A,
FGF13, etc.

Families with patients suspected to have GEFS+ should seek help from and epilepsy specialists and a
geneticist.

What is the syndrome of GEFS+?

This syndrome was first described by Drs Berkovic and Scheffer in 1997 and called Generalized Epilepsy
with Febrile Seizures Plus. In 2020, the G for “generalized” was replaced with “genetic” because patients
with this syndrome may not have “generalized” seizures but could also have focal seizures. A GEFS+
family is defined as a family with at least 2 or more individuals with GEFS+ seizures with at least one
family member with febrile seizures or febrile seizures plus (FS+).

Typically, seizures start between 3 months and 6 years of age, are triggered by fever, and are
generalized and short lasting for most patients. However instead of the common febrile seizure
syndrome where patients are likely to outgrow the fever-induced seizures by 6 years old, patients with
FS+ will continue to have febrile or non-febrile types of seizures after age 6 years.
There may be members in a family of GEFS+ family where some members have more severe forms of
epilepsy called Dravet syndrome or myoclonic atonic epilepsy.

What seizure types are seen?

The most common seizure types are typical febrile seizures, seen in approximately half of cases, or
febrile seizures plus, seen in approximately 1 in 4 cases. Although seizures are typically generalized tonic
clonic, patients can also have absence, myoclonic, atonic, myoclonic-atonic, or focal seizures. Dravet
syndrome and myoclonic atonic epilepsy represents the more severe end of the spectrum within the
GEFS+ phenotype.

Boys and girls are equally affected.

Is GEFS+ inherited?

GEFS+ is an inherited, genetic disorder. Multiple genes have been known to cause this condition.
Inheritance is generally autosomal dominant (passed on from one generation to the following) with
incomplete penetrance (may not see clinical effect in all affected individuals), but this may not be the
only situation. Approximately half of children born to a parent with GEFS+ are likely to have the
condition.

Variants (changes in genes) have been found in several genes including sodium channel subunits
(SCN1A, SCN2A, SCN1B, SCN9A) and GABAA–receptor gamma 2 subunit (GABRG2), STXBP1, and FGF13.
It is likely that other genes, as well as environmental factors, may modify the risk and severity of seizures
in this condition.

Diagnosis

GEFS+ is usually identified when the doctor takes a careful family history from someone who has febrile
seizures outside the normal age range. This may involve talking to immediate family members,
particularly to grandparents, who may remember their children or nieces and nephews having febrile
convulsions or other types of seizures as a child.

Investigations
An EEG (electroencephalogram) is often done and usually shows a normal background with generalized
discharges.

An MRI (magnetic resonance imaging) is often not required, but can be done if seizures are focal, or if
seizures appear to be more severe, and not responding to medication.

Genetic Testing

Genetic testing is not required for all families with this condition. You should discuss the need for
genetic testing with your health care provider. If done, genetic testing could be performed on blood or a
cheek swab. Your doctor may send either an epilepsy panel or whole exome sequencing.

Prognosis

Seizures typically stop by later childhood or adolescence and medications can usually be tapered off.
Development is usually normal. However, patients with Dravet syndrome or myoclonic atonic epilepsy
of Doose may not have a normal development and might have intellectual disability, learning or
behavioral disorders.

Management Options

Once a suspicion for GEFS+ is raised, you should seek care from a qualified epilepsy specialist.

Not every person will need to be placed on daily medication. Your doctor will discuss treatment options,
including rescue medications for repeated or prolonged febrile seizures. They will also discuss the pros
and cons of daily preventative medication.

Different rescue medicines for treating febrile seizures include rectal diazepam and intranasal
midazolam.

Repetitive febrile seizures or FS+ may need preventive treatment. Valproate, lamotrigine, levetiracetam,
or topiramate may be used for non-febrile generalized seizures, if these are frequent. Rare cases that
evolve to Dravet syndrome or myoclonic atonic epilepsy of Doose should be managed based on those
syndromes.
Rarely do patients need dietary therapy or surgery for seizures that are difficult to treat.