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Epilepsy, familial focal, with variable foci 3(FFEVF3)

MedGen UID:
934675
Concept ID:
C4310708
Disease or Syndrome
Synonym: FFEVF3
 
Gene (location): NPRL3 (16p13.3)
 
Monarch Initiative: MONDO:0014925
OMIM®: 617118

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
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.

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

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.

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.  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.
Focal cortical dysplasia, type IIA
MedGen UID:
1384182
Concept ID:
C4478700
Disease or Syndrome
A subtype of focal cortical dysplasia type II that is characterized by dysmorphic neurons, which present with a significantly enlarged cell body and nucleus, malorientation, abnormally distributed intracellular Nissl substance and cytoplasmic accumulation of neurofilament proteins.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

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

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
Li M, Huang Z, Zhang X, Duan Y, Jia Y, Ye J, Wang Y
Epileptic Disord 2019 Jun 1;21(3):289-294. doi: 10.1684/epd.2019.1066. PMID: 31225799
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
Spencer DD, Spencer SS
Neurol Clin 1985 May;3(2):313-30. PMID: 3927130
Wilson CL, Babb TL, Halgren E, Crandall PH
Brain 1983 Jun;106 (Pt 2):473-502. doi: 10.1093/brain/106.2.473. PMID: 6850279

Prognosis

Yang D, Wang J, Qin Z, Feng J, Mao C, Chen Y, Huang X, Ruan Y
Epilepsia Open 2024 Feb;9(1):33-40. Epub 2023 Nov 28 doi: 10.1002/epi4.12856. PMID: 37902097Free PMC Article
Dainelli A, Iacomino M, Rossato S, Bugin S, Traverso M, Severino M, Gustincich S, Capra V, Di Duca M, Zara F, Scala M, Striano P
Epilepsia Open 2023 Dec;8(4):1314-1330. Epub 2023 Sep 1 doi: 10.1002/epi4.12798. PMID: 37491868Free PMC Article
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

Clinical prediction guides

Yang D, Wang J, Qin Z, Feng J, Mao C, Chen Y, Huang X, Ruan Y
Epilepsia Open 2024 Feb;9(1):33-40. Epub 2023 Nov 28 doi: 10.1002/epi4.12856. PMID: 37902097Free PMC Article
Dainelli A, Iacomino M, Rossato S, Bugin S, Traverso M, Severino M, Gustincich S, Capra V, Di Duca M, Zara F, Scala M, Striano P
Epilepsia Open 2023 Dec;8(4):1314-1330. Epub 2023 Sep 1 doi: 10.1002/epi4.12798. PMID: 37491868Free PMC Article

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