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Epilepsy, familial focal, with variable foci 2(FFEVF2)

MedGen UID:
934676
Concept ID:
C4310709
Disease or Syndrome
Synonym: FFEVF2
 
Gene (location): NPRL2 (3p21.31)
 
Monarch Initiative: MONDO:0014924
OMIM®: 617116

Definition

Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and nocturnal frontal lobe epilepsy (NFLE). A subset of patients have structural brain abnormalities, particularly focal cortical dysplasia (FCD). There is significant incomplete penetrance, with many unaffected mutation carriers within a family (summary by Ricos et al., 2016). For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364). [from OMIM]

Additional description

From MedlinePlus Genetics
Most people with FFEVF are intellectually normal, and there are no problems with their brain function between seizures. However, some people with FFEVF have developed psychiatric disorders (such as schizophrenia), behavioral problems, or intellectual disability. It is unclear whether these additional features are directly related to epilepsy in these individuals.

Some individuals with FFEVF also have a brain malformation called focal cortical dysplasia. Seizures in these individuals are typically not well-controlled with medication.

Among family members with FFEVF, individuals may not have the same brain region affected (variable foci), meaning that one person's seizures may not begin in the same part of the brain as their affected relative.

Familial focal epilepsy with variable foci (FFEVF) is an uncommon form of recurrent seizures (epilepsy) that runs in families. Seizures associated with FFEVF can begin at any time from infancy to adulthood. The seizures are described as focal or partial, which means they begin in one region of the brain and do not cause a loss of consciousness. In more than 70 percent of affected individuals, these seizures begin in one of two areas of the brain, either the temporal lobe or the frontal lobe. The region of the brain where the seizures start tends to stay the same over time. In rare instances, seizure activity that starts in one area spreads to affect the entire brain and causes a loss of consciousness, muscle stiffening, and rhythmic jerking. Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures.  https://medlineplus.gov/genetics/condition/familial-focal-epilepsy-with-variable-foci

Clinical features

From HPO
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.
Focal cortical dysplasia
MedGen UID:
853938
Concept ID:
C2938983
Congenital Abnormality
A type of malformation of cortical development that primarily affects areas of neocortex. It can be identified on conventional magnetic resonance imaging as focal cortical thickening, abnormal gyration, and blurring between gray and white matter, often associated with clusters of heterotopic neurons.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Wang Z, Guo J, van 't Klooster M, Hoogteijling S, Jacobs J, Zijlmans M
Neurology 2024 May 14;102(9):e209216. Epub 2024 Apr 1 doi: 10.1212/WNL.0000000000209216. PMID: 38560817
Auerbach DS, Jones J, Clawson BC, Offord J, Lenk GM, Ogiwara I, Yamakawa K, Meisler MH, Parent JM, Isom LL
PLoS One 2013;8(10):e77843. Epub 2013 Oct 14 doi: 10.1371/journal.pone.0077843. PMID: 24155976Free PMC Article
Kokkinos V, Koupparis AM, Tsiptsios D, Kostopoulos GK, Koutroumanidis M
Epileptic Disord 2013 Mar;15(1):14-26. doi: 10.1684/epd.2013.0561. PMID: 23702456
Sadler RM, Blume WT
Epilepsia 1989 Mar-Apr;30(2):143-6. doi: 10.1111/j.1528-1157.1989.tb05446.x. PMID: 2494040

Diagnosis

Myers KA
Continuum (Minneap Minn) 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962
Zhang J, Shen Y, Yang Z, Yang F, Li Y, Yu B, Chen W, Gan J
J Hum Genet 2022 Feb;67(2):79-85. Epub 2021 Aug 11 doi: 10.1038/s10038-021-00969-z. PMID: 34376795Free PMC Article
Scheffer IE, Heron SE, Regan BM, Mandelstam S, Crompton DE, Hodgson BL, Licchetta L, Provini F, Bisulli F, Vadlamudi L, Gecz J, Connelly A, Tinuper P, Ricos MG, Berkovic SF, Dibbens LM
Ann Neurol 2014 May;75(5):782-7. Epub 2014 Apr 14 doi: 10.1002/ana.24126. PMID: 24585383
Wang X, Lu Y
Front Biosci 2008 Jan 1;13:3159-67. doi: 10.2741/2917. PMID: 17981785
Spencer DD, Spencer SS
Neurol Clin 1985 May;3(2):313-30. PMID: 3927130

Therapy

Kalinin VV, Zheleznova EV
Epilepsy Behav 2007 Sep;11(2):185-91. Epub 2007 Jun 18 doi: 10.1016/j.yebeh.2007.04.014. PMID: 17573242

Prognosis

Wang Z, Guo J, van 't Klooster M, Hoogteijling S, Jacobs J, Zijlmans M
Neurology 2024 May 14;102(9):e209216. Epub 2024 Apr 1 doi: 10.1212/WNL.0000000000209216. PMID: 38560817
Myers KA
Continuum (Minneap Minn) 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962
Zhang J, Shen Y, Yang Z, Yang F, Li Y, Yu B, Chen W, Gan J
J Hum Genet 2022 Feb;67(2):79-85. Epub 2021 Aug 11 doi: 10.1038/s10038-021-00969-z. PMID: 34376795Free PMC Article
Striano P, Serioli E, Santulli L, Manna I, Labate A, Dazzo E, Pasini E, Gambardella A, Michelucci R, Striano S, Nobile C
Epilepsia 2015 Oct;56(10):e168-71. Epub 2015 Jul 27 doi: 10.1111/epi.13094. PMID: 26216793

Clinical prediction guides

Wang Z, Guo J, van 't Klooster M, Hoogteijling S, Jacobs J, Zijlmans M
Neurology 2024 May 14;102(9):e209216. Epub 2024 Apr 1 doi: 10.1212/WNL.0000000000209216. PMID: 38560817
Striano P, Serioli E, Santulli L, Manna I, Labate A, Dazzo E, Pasini E, Gambardella A, Michelucci R, Striano S, Nobile C
Epilepsia 2015 Oct;56(10):e168-71. Epub 2015 Jul 27 doi: 10.1111/epi.13094. PMID: 26216793
Auerbach DS, Jones J, Clawson BC, Offord J, Lenk GM, Ogiwara I, Yamakawa K, Meisler MH, Parent JM, Isom LL
PLoS One 2013;8(10):e77843. Epub 2013 Oct 14 doi: 10.1371/journal.pone.0077843. PMID: 24155976Free PMC Article
Kalinin VV, Zheleznova EV
Epilepsy Behav 2007 Sep;11(2):185-91. Epub 2007 Jun 18 doi: 10.1016/j.yebeh.2007.04.014. PMID: 17573242

Recent systematic reviews

Wang Z, Guo J, van 't Klooster M, Hoogteijling S, Jacobs J, Zijlmans M
Neurology 2024 May 14;102(9):e209216. Epub 2024 Apr 1 doi: 10.1212/WNL.0000000000209216. PMID: 38560817

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