SNP Shot: Genomic Insights

Genetic epilepsy with febrile seizures plus (GEFS+) encompasses a range of seizure disorders that vary in severity. This condition is typically identified in families where members experience both febrile seizures (triggered by high fever) and other types of recurrent seizures (epilepsy), including those unrelated to fever (afebrile seizures). While generalized seizures, affecting both brain hemispheres, are more common, some individuals with GEFS+ also experience partial seizures, which affect only one side of the brain. Common seizure types associated with GEFS+ include myoclonic seizures (involuntary muscle twitches), atonic seizures (sudden loss of muscle tone), and absence seizures (brief losses of consciousness resembling staring spells).

The mildest and most frequent manifestation of GEFS+ is simple febrile seizures, typically starting in infancy and resolving by age 5. When febrile seizures persist beyond age 5, or when other seizure types emerge, the condition is classified as febrile seizures plus (FS+). In FS+, seizures usually cease by early adolescence.

Dravet syndrome, also known as severe myoclonic epilepsy of infancy (SMEI), is frequently considered a severe form within the GEFS+ spectrum. Infants with Dravet syndrome commonly experience prolonged, fever-induced seizures (status epilepticus). In early childhood, additional seizure types, including afebrile seizures like myoclonic or absence seizures, may develop. These seizures in Dravet syndrome are often difficult to control with medication and may worsen over time. Cognitive decline is also a characteristic feature. While initial development is usually normal, it plateaus, and some children lose previously acquired skills (developmental regression). Many individuals with Dravet syndrome experience difficulties with coordination (ataxia) and intellectual disability.

Some individuals with GEFS+ exhibit seizure disorders of intermediate severity, not neatly fitting into the categories of simple febrile seizures, FS+, or Dravet syndrome.

Within families affected by GEFS+, the presentation of febrile seizures and epilepsy can vary among members. For instance, one family member might only experience febrile seizures, while another might also have myoclonic epilepsy. While GEFS+ is typically diagnosed within a family context, it can also arise in individuals without any prior family history of the condition.

Inheritance:

GEFS+ typically follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene is needed in each cell to cause the disorder. In some instances, the affected individual inherits the mutation from a parent who also has GEFS+. However, GEFS+ can also result from new (de novo) mutations, occurring in individuals with no family history of the condition. Dravet syndrome is almost always caused by de novo mutations, but it can be inherited from a parent with a milder form of GEFS+. Other forms of GEFS+ are usually inherited from an affected parent. In rare cases, Dravet syndrome or other forms of GEFS+ can be inherited from a parent who has somatic mosaicism. Somatic mosaicism describes a situation where some of the body's cells contain the gene mutation, while others do not. A parent with mosaicism may exhibit milder symptoms or no symptoms of GEFS+.