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Generalized epilepsy with febrile seizures plus, type 12(GEFSP12; GEFS+12)

MedGen UID:
1854923
Concept ID:
C5935592
Disease or Syndrome
Synonym: GEFS+, TYPE 12
 
Gene (location): SLC32A1 (20q11.23)
 
Monarch Initiative: MONDO:0958324
OMIM®: 620755

Definition

Generalized epilepsy with febrile seizures plus type 12 (GEFSP12) is characterized by variable types of seizures, most often febrile seizures, sometimes combined with additional nonfebrile seizures, including focal or generalized seizures. Some mutation carriers do not have febrile seizures, but demonstrate focal, generalized, rare myoclonic-atonic seizures, or nonspecific epilepsy consistent with idiopathic generalized epilepsy (EIG; see 600669). The transmission pattern of GEFSP12 is consistent with autosomal dominant inheritance with variable expressivity within families and incomplete penetrance (Heron et al., 2021). For a discussion of genetic heterogeneity of GEFS+, see 604233. [from OMIM]

Clinical features

From HPO
Sudden unexpected death in epilepsy
MedGen UID:
930396
Concept ID:
C4304727
Finding
Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected, witnessed or unwitnessed, non-traumatic and non-drowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus, in which postmortem examination has not revealed a cause of death.
Febrile seizure (within the age range of 3 months to 6 years)
MedGen UID:
3232
Concept ID:
C0009952
Disease or Syndrome
A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
Myoclonic-astatic epilepsy
MedGen UID:
98284
Concept ID:
C0393702
Disease or Syndrome
A generalized myoclonic-atonic seizure is a type of generalized motor seizure characterized by a myoclonic jerk followed by an atonic motor component.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Paroxysmal dyskinesia
MedGen UID:
156242
Concept ID:
C0752210
Disease or Syndrome
Episodic bouts of involuntary movements with dystonic, choreic, ballistic movements, or a combination thereof. There is no loss of consciousness during the attacks.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Bilateral tonic-clonic seizure with generalized onset
MedGen UID:
1368929
Concept ID:
C4476643
Sign or Symptom
A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure.

Recent clinical studies

Etiology

van Hugte EJH, Lewerissa EI, Wu KM, Scheefhals N, Parodi G, van Voorst TW, Puvogel S, Kogo N, Keller JM, Frega M, Schubert D, Schelhaas HJ, Verhoeven J, Majoie M, van Bokhoven H, Nadif Kasri N
Brain 2023 Dec 1;146(12):5153-5167. doi: 10.1093/brain/awad245. PMID: 37467479Free PMC Article

Diagnosis

van Hugte EJH, Lewerissa EI, Wu KM, Scheefhals N, Parodi G, van Voorst TW, Puvogel S, Kogo N, Keller JM, Frega M, Schubert D, Schelhaas HJ, Verhoeven J, Majoie M, van Bokhoven H, Nadif Kasri N
Brain 2023 Dec 1;146(12):5153-5167. doi: 10.1093/brain/awad245. PMID: 37467479Free PMC Article
Marini C, Scheffer IE, Nabbout R, Mei D, Cox K, Dibbens LM, McMahon JM, Iona X, Carpintero RS, Elia M, Cilio MR, Specchio N, Giordano L, Striano P, Gennaro E, Cross JH, Kivity S, Neufeld MY, Afawi Z, Andermann E, Keene D, Dulac O, Zara F, Berkovic SF, Guerrini R, Mulley JC
Epilepsia 2009 Jul;50(7):1670-8. Epub 2009 Mar 12 doi: 10.1111/j.1528-1167.2009.02013.x. PMID: 19400878
Ceulemans BP, Claes LR, Lagae LG
Pediatr Neurol 2004 Apr;30(4):236-43. doi: 10.1016/j.pediatrneurol.2003.10.012. PMID: 15087100
Kamiya K, Kaneda M, Sugawara T, Mazaki E, Okamura N, Montal M, Makita N, Tanaka M, Fukushima K, Fujiwara T, Inoue Y, Yamakawa K
J Neurosci 2004 Mar 17;24(11):2690-8. doi: 10.1523/JNEUROSCI.3089-03.2004. PMID: 15028761Free PMC Article

Prognosis

van Hugte EJH, Lewerissa EI, Wu KM, Scheefhals N, Parodi G, van Voorst TW, Puvogel S, Kogo N, Keller JM, Frega M, Schubert D, Schelhaas HJ, Verhoeven J, Majoie M, van Bokhoven H, Nadif Kasri N
Brain 2023 Dec 1;146(12):5153-5167. doi: 10.1093/brain/awad245. PMID: 37467479Free PMC Article
Cossette P, Loukas A, Lafrenière RG, Rochefort D, Harvey-Girard E, Ragsdale DS, Dunn RJ, Rouleau GA
Epilepsy Res 2003 Feb;53(1-2):107-17. doi: 10.1016/s0920-1211(02)00259-0. PMID: 12576172

Clinical prediction guides

van Hugte EJH, Lewerissa EI, Wu KM, Scheefhals N, Parodi G, van Voorst TW, Puvogel S, Kogo N, Keller JM, Frega M, Schubert D, Schelhaas HJ, Verhoeven J, Majoie M, van Bokhoven H, Nadif Kasri N
Brain 2023 Dec 1;146(12):5153-5167. doi: 10.1093/brain/awad245. PMID: 37467479Free PMC Article
Ceulemans BP, Claes LR, Lagae LG
Pediatr Neurol 2004 Apr;30(4):236-43. doi: 10.1016/j.pediatrneurol.2003.10.012. PMID: 15087100
Cossette P, Loukas A, Lafrenière RG, Rochefort D, Harvey-Girard E, Ragsdale DS, Dunn RJ, Rouleau GA
Epilepsy Res 2003 Feb;53(1-2):107-17. doi: 10.1016/s0920-1211(02)00259-0. PMID: 12576172

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