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Epilepsy, familial focal, with variable foci 4(FFEVF4)

MedGen UID:
1644614
Concept ID:
C4693694
Disease or Syndrome
Synonym: FFEVF4
 
Gene (location): SCN3A (2q24.3)
 
Monarch Initiative: MONDO:0054776
OMIM®: 617935

Disease characteristics

Excerpted from the GeneReview: SCN3A-Related Neurodevelopmental Disorder
SCN3A-related neurodevelopmental disorder (SCN3A-ND) encompasses a spectrum of clinical severity associated with epilepsy and/or brain malformation. Affected individuals may have (a) developmental and epileptic encephalopathy (DEE) (i.e., intractable seizures with developmental delays associated with ongoing epileptiform EEG activity) with or without malformations of cortical development; or (b) malformations of cortical development with or without mild focal epilepsy. Some degree of early childhood developmental delay is seen in all affected individuals; the severity varies widely, ranging from isolated speech delay to severe developmental delay. Infantile hypotonia is common but may be mild or absent in those without DEE. In those with DEE, seizure onset is typically in the first six to 12 months of life. A variety of seizure types have been described. Seizures remain intractable to multiple anti-seizure medications in approximately 50% of individuals with DEE without malformations of cortical development (MCD) and in 90% of individuals with DEE and MCD. Seizures may be absent or infrequent in those without DEE. Brain MRI findings range from normal to showing thinning or hypoplasia of the corpus callosum, to various malformations of cortical development. Autonomic dysregulation, oromotor dysfunction leading to the need for gastrostomy tube placement, progressive microcephaly, hyperkinetic movement disorder, and cortical visual impairment can also be seen in those with DEE. [from GeneReviews]
Authors:
Katherine L Helbig  |  Ethan M Goldberg   view full author information

Additional description

From OMIM
Familial focal epilepsy with variable foci-4 (FFEVF4) is an autosomal dominant seizure disorder characterized by onset of focal seizures in the first years of life. Some patients may have secondary generalization and/or mild developmental deficits (summary by Vanoye et al., 2014). For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364).  http://www.omim.org/entry/617935

Clinical features

From HPO
Intellectual disability, borderline
MedGen UID:
507499
Concept ID:
C0006009
Finding
Borderline intellectual disability is defined as an intelligence quotient (IQ) in the range of 70-85.
Abnormal autonomic nervous system physiology
MedGen UID:
8511
Concept ID:
C0013363
Disease or Syndrome
A functional abnormality of the autonomic nervous system.
Simple febrile seizure
MedGen UID:
101773
Concept ID:
C0149886
Disease or Syndrome
A short generalized seizure, of a duration of <15 min, not recurring within 24 h, occurring during a febrile episode not caused by an acute disease of the nervous system intracranial infection or severe metabolic disturbance.
Clonic seizure
MedGen UID:
66708
Concept ID:
C0234535
Disease or Syndrome
A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Small face
MedGen UID:
343376
Concept ID:
C1855538
Finding
A face that is short and narrow.

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
Ishida S, Picard F, Rudolf G, Noé E, Achaz G, Thomas P, Genton P, Mundwiller E, Wolff M, Marescaux C, Miles R, Baulac M, Hirsch E, Leguern E, Baulac S
Nat Genet 2013 May;45(5):552-5. Epub 2013 Mar 31 doi: 10.1038/ng.2601. PMID: 23542701Free PMC Article
Jehi LE, Silveira DC, Bingaman W, Najm I
J Neurosurg 2010 Dec;113(6):1186-94. Epub 2010 Sep 10 doi: 10.3171/2010.8.JNS10180. PMID: 20831360

Diagnosis

Martin C, Meloche C, Rioux MF, Nguyen DK, Carmant L, Andermann E, Gravel M, Cossette P
Clin Genet 2014 Dec;86(6):570-4. Epub 2013 Nov 27 doi: 10.1111/cge.12311. PMID: 24283814
Ishida S, Picard F, Rudolf G, Noé E, Achaz G, Thomas P, Genton P, Mundwiller E, Wolff M, Marescaux C, Miles R, Baulac M, Hirsch E, Leguern E, Baulac S
Nat Genet 2013 May;45(5):552-5. Epub 2013 Mar 31 doi: 10.1038/ng.2601. PMID: 23542701Free PMC Article
Hayman M, Scheffer IE, Chinvarun Y, Berlangieri SU, Berkovic SF
Neurology 1997 Oct;49(4):969-75. doi: 10.1212/wnl.49.4.969. PMID: 9339675
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

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
Martin C, Meloche C, Rioux MF, Nguyen DK, Carmant L, Andermann E, Gravel M, Cossette P
Clin Genet 2014 Dec;86(6):570-4. Epub 2013 Nov 27 doi: 10.1111/cge.12311. PMID: 24283814
Jehi LE, Silveira DC, Bingaman W, Najm I
J Neurosurg 2010 Dec;113(6):1186-94. Epub 2010 Sep 10 doi: 10.3171/2010.8.JNS10180. PMID: 20831360

Clinical prediction guides

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
Wang Y, Yu P, Zhu G, Wu X, Ding D, Hong Z
PLoS One 2023;18(4):e0284924. Epub 2023 Apr 26 doi: 10.1371/journal.pone.0284924. PMID: 37099548Free PMC Article
Martin C, Meloche C, Rioux MF, Nguyen DK, Carmant L, Andermann E, Gravel M, Cossette P
Clin Genet 2014 Dec;86(6):570-4. Epub 2013 Nov 27 doi: 10.1111/cge.12311. PMID: 24283814
Jehi LE, Silveira DC, Bingaman W, Najm I
J Neurosurg 2010 Dec;113(6):1186-94. Epub 2010 Sep 10 doi: 10.3171/2010.8.JNS10180. PMID: 20831360

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