Familial focal epilepsy with variable foci …

Eliane Kobayashi MD PhD

Epilepsy & Seizures

Updated 08.20.2024
Released 07.14.2009
Expires For CME 08.20.2027

Familial focal epilepsy with variable foci

Author: Eliane Kobayashi MD PhD

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Editor: Jerome Engel Jr MD PhD

Familial focal epilepsy with variable foci

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Introduction

Overview

In this article, the author highlights clinical and genetic findings about NPRL2- and NPRL3-related epilepsies.

Key points

	• Diagnosis of familial focal epilepsy with variable foci depends on evaluation of all family members with a history of seizures, most having temporal or frontal epilepsy.
	• Seizure focus is variable across affected individuals but remains the same within individual patients.
	• Mutations and variants in the GATOR1 complex genes (most frequently DEPDC5) have been identified in various familial focal epilepsy with variable foci kindreds, but also in other focal familial epilepsy kindreds, including patients with familial focal cortical dysplasia and sporadic epilepsy.
	• Pharmacoresistance and malformations of cortical development can occur and have been most often associated with NPLR3 and DEPDC5 gene mutations and variants.

Historical note and terminology

Formerly known as familial partial epilepsy with variable foci, autosomal dominant familial focal epilepsy with variable foci (FFEVF) is a unique epilepsy syndrome first reported in an Australian kindred (67) after other more homogeneous familial focal epilepsy syndromes, such as familial temporal and frontal epilepsies, had been described (13; 66; 54).

Familial focal epilepsy with variable foci is unique among the familial focal epilepsies because different clinical and EEG features can be observed in different family members. On the other hand, the epileptic focus in any one individual remains the same. This syndrome with variable foci was included in the diagnostic scheme for epileptic syndromes proposed by the International League Against Epilepsy (26; 27).

Familial focal epilepsy with variable foci shows an autosomal dominant inheritance pattern with approximately 70% penetrance. Two different loci had been initially associated with this syndrome; the first suggestive linkage was found on chromosome 2q (67), but posterior reanalysis excluded such findings (39). Indeed, no other tested families showed linkage to chromosome 2q (51). Thus, the second described and proven linkage has been established on chromosome 22q (79; 78; 17; 15; 51; 39).

FFEVF can be defined based on family rather than individual phenotypes. The occurrence of at least two different focal epilepsy syndromes in first- and second-degree relatives, with or without identifiable structural brain abnormality and segregating in a sufficient number of individuals in more than one generation, can be suggestive of FFEVF. Nevertheless, many small families in which the diagnosis and the inheritance pattern could not be confirmed share common mutations and variants to definite FFEVF large kindreds (36; 25; 48).

The first gene was finally identified in 2013, with different groups worldwide reporting mutations and variants in the DEPDC5 [disheveled Egl-10 and pleckstrin (DEP) domain containing protein 5] gene on ch22q. This was found not only in familial focal epilepsy with variable foci, but also in other familial focal epilepsies (25; 36; 48; 72; 63; 61) and epileptic spasms (18). In the families studied, the frequency of DEPDC5 mutations and variants was observed as 5% to 37% (11).

Later, mutations and variants in NPRL2 (nitrogen permease regulator 2-like protein) and NPRL3 (nitrogen permease regulator 3-like protein) genes, which, similar to DEPDC5 belong to GATOR1 (GAP activity toward RAGs complex 1) and are regulators of mammalian target of rapamycin (mTOR), were found in 2% to 11% of probands of families with focal epilepsies with or without malformations of cortical development (63; 68; 76; 47; 73). Taken together, these findings gave rise to the conceptualization of GATORopathy or mTORopathy as an etiology for familial (and later also associated with sporadic) focal epilepsies, with or without associated malformations of cortical development (50). Approximately 55% of patients identified with a GATOR1 variant or mutation present with a family history for epilepsy (07).

Clinical manifestations

Presentation and course

Affected family members may present with different types of focal epilepsy, which are, however, invariable within each subject. Frontal lobe seizures are the most frequent manifestation, but they have a different pattern in familial focal epilepsy with variable foci as compared to that observed in autosomal dominant sleep-related hyperkinetic/hypermotor epilepsy or ADSHE (previously known as autosomal dominant nocturnal frontal lobe epilepsy): the seizures are less frequent, at times clustering, focal aware seizures are rare, and daytime seizures as well as focal to bilateral tonic-clonic seizures are more frequently reported (15). Age at seizure onset is variable, usually occurring in the first 3 decades, with two peaks at approximately 5 and 25 years of age (79; 78). Although temporal lobe seizures are also commonly found, centroparietal and occipital seizures are less frequent. There is marked intrafamilial heterogeneity in seizure severity and outcome.

Baldassari and colleagues detailed a large cohort of 73 families in which the probands were diagnosed with GATOR1 complex mutations and variants (07). The age at epilepsy onset ranged from first days of life to 16 years (mean: 4.4 years), with 30% occurring within the first year. Most (68%) patients presented with focal seizures, and almost half of them had predominantly seizures during sleep: 36% with sleep-related hypermotor seizures, 16% with frontal lobe seizures, 32% with focal seizures with undetermined origin, and 10% with infantile spasms.

FFEVF most often has a benign clinical course, although patients with refractory seizures have been reported, particularly patients with NPRL3-related epilepsy (07; 09; 20). Drug-resistant seizures developed in 54% of patients, being even more frequent (65%) among patients with sleep-related hypermotor seizures. Interestingly, 60% of these patients had cognitive impairment and/or psychiatric comorbidities, and this was even more frequent (76%) in patients with early onset (≤1 year of age). In contrast, cognitive dysfunction was reported in 44% (mostly mild to moderate: 20%), whereas learning or language disabilities/delay were reported in 15% of probands, also more prevalent among patients with early epilepsy onset.

A few patients have undergone resective surgery, including temporal and frontal resections (78; 15; 76; 07). Patients with an underlying DEPDC5 variant or mutation and focal cortical dysplasia confirmed in neuropathology had a good reported postoperative outcome (07). In one case report of a proband with familial focal epilepsy with variable foci and stereotactic EEG confirmation of two independent seizure foci (left hippocampus and left orbitofrontal cortex), laser interstitial thermal therapy resulted in seizure freedom (02).

NPRL3 gene mutations and variants can more frequently present with drug-resistant seizures, particularly when associated with focal cortical dysplasia (68). From approximately 60 patients with NPRL3-related epilepsy (including two with FFEVF) reported in the literature, 10 out of 15 (73%) patients who underwent epilepsy surgery became seizure free. Focal cortical dysplasia type IIa is the most frequent histopathological finding in operated patients with NPRL3-related epilepsy (20). Patients with refractory seizures and focal cortical dysplasia type IIa, associated with a DEPDC5 mutation, have also been operated with good postoperative results to date (12; 65).

A case report on the use of everolimus for patients with refractory epilepsy with variants in DEPDC5 (N=4) and NPRL3 (N=1) has been published (50). With the primary outcome measure being change in mean monthly seizure frequency, the authors observed that the patient with NPRL3-related epilepsy worsened compared to baseline, whereas all four patients with DEPDC5-related epilepsy significantly improved, with reduced seizures (74% to 86%).

Prognosis and complications

Sudden unexpected death in epilepsy (SUDEP) has been reported in patients with FFEVF. In a large cohort of 73 families, SUDEP occurred in nine individuals belonging to eight families: one proband had definite SUDEP, and eight affected relatives had probable SUDEP (mean age at death: 36.8 years; range: 19 to 59 years) (07). SUDEP was mostly associated with DEPDC5 pathogenic null variants (including two deaths occurring in one family), with more recent reports of patients with NPRL3 variants having also died from SUDEP (07; 20).

In one study, including patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3 and mice models, Bacq and colleagues found no evidence of structural nor functional cardiac damage as contributory factor to sudden unexpected death in epilepsy (04). The study included three SUDEP patients and six individuals with a family history of SUDEP. Clinical work up, including Holter, echocardiogram, and electrocardiogram, indicated normal cardiac function in these patients. Furthermore, there was no evidence of cardiac injury at autopsy in one postmortem DEPDC5 sudden unexpected death in epilepsy case. The authors used two Depdc5 mouse strains: a human HA-tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5c/-). Simultaneous EEG-ECG recording on Depdc5c/- mice failed to demonstrate any cardiac arrhythmia preceding sudden unexpected death in epilepsy following spontaneous seizures.

Clinical vignette

Xiong and colleagues detailed clinical and genetic investigation of two large kindreds found to have common ancestors of French-Canadian origin, including 63 family members with seizures or suspected seizures (79; 78). A description of these individuals is out of the scope of this clinical summary and can be found in these previous publications. For illustrative purposes, we provide the details of the proband of one of these families.

At the time of identification, the proband of pedigree number 22 was a 13-year-old boy with refractory seizures since the age of 5. Previously used antiseizure medications included carbamazepine, phenytoin, clobazam, lamotrigine, valproate, primidone, and vigabatrin. Most often, seizures occurred in the morning or late in the evening, without clustering, once every 1 or 2 weeks. He had two types of seizures: (1) deep breathing and lip smacking followed by head turn to the right, tonic flexion of the left arm and right hand automatisms (tonic extension of the left leg can occur), and mild postictal confusion; (2) occurring during sleep with awakening, trunk movements (rocking back and forth in bed) with occasional pelvic thrusting, scissor-like movements, and groaning sounds with deep breaths.

His general physical and neurologic examinations were normal. Video-EEG monitoring revealed bilateral frontal onset of seizures with right-sided predominance. Interictal EEG showed an epileptiform disturbance over the right hemisphere, involving the fronto-centro-parietal and temporal regions, with spikes and sharp waves observed mainly in the right frontal and temporal regions. MRI, including volumetric studies, was normal, although the right hippocampus appeared bigger than the left. Dysfunction over the right temporal region was revealed by 1H-MRS (reduction of N-acetylaspartate) and by [18F]FDG-PET (hypometabolism). Neuropsychological evaluation demonstrated no cognitive dysfunction, a full-scale IQ of 118, and suggestion of left-sided speech representation.

Biological basis

Etiology and pathogenesis

The etiology of familial focal epilepsy with variable foci started to be clarified with the description of mutations and variants in the DEPDC5 gene in ch22q in approximately 37% of families studied (11). However, as such mutations and variants have also been found in smaller families including those with ADSHE, rolandic epilepsy, temporal lobe epilepsy, epileptic spasms, as well as patients with no family history of seizures, their specificity in how they lead to the unique presentation in familial focal epilepsy with variable foci remains to be further elucidated (36; 43; 48; 60; 12; 18; 24; 61; 65; 72; 63; 74; 82).

The identification of mutations and variants in genes encoding other components of GATOR1 complex, which includes not only DEPDC5 but also NPRL2 and NPRL3, suggests that the resulting pathogenesis and pathophysiology derive from dysregulation of the mTOR pathway, as GATOR1 complex is involved in the inhibition of mTOR complex 1 (06; 11).

The DEPDC5 gene encodes a protein expressed in neurons throughout brain development (48). The protein has a DEP (Dishevelled, Egl-10, and Pleckstrin) domain that is found in proteins involved in G-protein signaling pathways. Most of the 140 different variants identified correspond to loss-of-function mutations and variants (67%), 24 of which were found in unrelated cases, suggesting mutational hotspots or founder effects. Less frequently, missense (27%), splice-region variants (4%), and in-frame indels (1%) have been reported (07).

In a series of 19 autosomal dominant families with focal epilepsy, four had FFEVF (59). These families have been reevaluated and showed linkage to chromosome 22q12, with mutations and variants in the DEPDC5 gene found in 37% of them (36).

Among approximately 183 patients who have been reported with a GATOR1 mutation or variant, DEPDC5 was found to be the most frequent (155, 85%) and NPRL2 the less prevalent (10 patients) (07). Baldassari and colleagues highlight that this is likely due to DEPDC5 transcript being longer (5551bp) than NPRL2 (1700bp) and NPRL3 (2881bp), and the latter two having been less frequently tested than DEPDC5 due to their more recent discovery (07). To date, a total of 33 patients with NPRL2-related epilepsy have been identified (81).

Indeed, additional patients have been subsequently reported, and in a review of NPRL3-related epilepsies, a total of 124 patients were identified in the literature, mostly with pathogenic variants (20; 75; 80). NPRL2 and NPRL3 mutations and variants have been found in familial and nonfamilial cases, with or without focal cortical dysplasia (41; 63; 68; 76; 07; 47; 73). Malformation of cortical development was identified in 23 out of 68 patients for whom brain MRI results were reported: 18 of 23 with focal cortical dysplasia, three with hemimegalencephaly, one with periventricular heterotopia, and one with polymicrogyria (80).

From the French Canadian familial focal epilepsy with variable foci cohort, DEPDC5 mutations and variations were found in 5% of familial and sporadic focal epilepsy cases (4/79), with identification of a founder mutation specific to this population (48). DEPDC5 loss-of-function mutations and variants were found in 13% of these families with a presentation of ADSHE.

The identification of DEPDC5 mutations and variants in patients with malformations of cortical development is a major discovery, as clinical observation of focal cortical dysplasia in the context of familial epilepsies had been noted (12; 24; 65). In addition to familial focal cortical dysplasia associated with DEPDC5 mutations and variants, DEPDC5 mutations and variants have also been found in patients with sporadic focal cortical dysplasia, hemimegalencephaly, and pachygyria (24; 19).

In a large phenotyping study including 303 families with epilepsy, seven of 62 (11.3%) kindreds with focal epilepsy were classified as familial focal epilepsy with variable foci, many of which had been tested negative for DEPDC5 mutations and variants (28). DEPDC5 was the only gene with study-wide significance in an exome sequence study derived from the Epilepsy Phenome/Genome Project and Epi4K Consortium comparing individuals with familial genetic generalized epilepsy (N=640), familial nonacquired focal epilepsy (N=525), and 3877 controls (28). In addition to DEPDC5, ultra-rare deleterious variants were identified in four other genes previously known to be associated with epilepsy (LGI1, PCDH19, SCN1A, and GRIN2A), altogether contributing to the risk of epilepsy in approximately 8% of individuals with familial nonacquired focal epilepsy.

The mechanisms by which mutations and variations in the DEPDC5 gene can present as different types of focal epilepsy within the same family are intriguing (10). The same questions remain for the presence and type of underlying malformation of cortical development. The two-hit somatic mutation hypothesis has been demonstrated in two independent studies, which included in utero electroporation to create focal somatic DEPDC5 deletion in the rat embryonic brain (34; 62). Interestingly, this resulted in spontaneous seizures with focal pathological and electroclinical features as seen in patients with focal cortical dysplasia type IIa (34). This second hit mutation might be cell-specific, such as in dysmorphic neurons of focal cortical dysplasia type IIa (44). The role of DEPDC5 in the development of epileptogenesis by affecting excitatory synapses and increasing expression of glutamate receptors could underlie the mechanism through which these mutations and variants relate to epilepsy phenotypes and mTOR hyperactivation (23).

Many studies on surgical brain tissue have provided important information to date. Analysis of freshly frozen tissue from surgery in a patient with refractory seizures demonstrated a mutation gradient with a higher rate of mosaicism in the seizure-onset zone than in the surrounding epileptogenic zone (62).

In a cohort of surgical specimens derived from 80 children with neuropathological diagnosis of focal cortical dysplasia and hemimegalencephaly, targeted gene sequencing identified variants in 29% of focal cortical dysplasia type I patients and 63% of focal cortical dysplasia type II or hemimegalencephaly patients (07b). Germline, somatic, and two-hit loss-of-function variants in DEPDC5 were found exclusively in the latter group of patients. In a study of eight operated children diagnosed with DEPDC5 and NPRL3 loss-of-function variants, focal cortical dysplasia was also the most common neuropathological finding, when available (64).

Pathogenic mutations and variants were identified in 32% of 446 tissues samples from 232 epilepsy patients with various underlying neuropathological diagnosis, including DEPDC5 (69). Targeted panel deep sequencing on paired blood and brain-derived genomic DNA from operated patients with bottom of the sulcus dysplasia revealed pathogenic germline DEPDC5 and NPRL3 variants in two of 20 patients (45).

Animal models provide useful insight into pathophysiological mechanisms of these gene alterations. A knockout DEPDC5 mouse generated using targeted CRISPR mutagenesis revealed homozygous phenotypes that support mTORC1 hyperactivation as a pathogenic mechanism underlying DEPDC5 loss of function in humans (35). Heterozygous mice had normal phenotypes. The mTORC1 hyperactivation mechanism has been further demonstrated by Ribierre and colleagues, who performed a single intraperitoneal injection of rapamycin into pregnant dams at E15, preventing the neuronal migration disorder seen in DEPDC5 knockout embryos (ie, cells retained into the ventricular and subventricular zones at E18.5) (62).

Mice in which NPRL2 and NPRL3 were conditionally deleted from the dorsal telencephalon present with spontaneous seizures and dysmorphic enlarged neuronal cells with increased mTORC1 signaling, similar to Depdc5-cKO mice (37). Chronic postnatal administration of rapamycin had a therapeutic effect on clinical presentation (prolonging survival period and inhibiting seizure occurrence), which was, however, short-lasting after cessation of rapamycin as compared to that observed in Depdc5-cKO mice.

The finding of DEPDC5 and NPRL2 mutations and variants in patients who had definite or probable sudden unexpected death in epilepsy represents another important clinical association that warrants further understanding on the pathogenesis of GATOR1 genes (53; 05; 76; 07). In three DEPDC5 knockout mice, a single seizure was followed by sudden death, further indicating that focal brain mosaic knockout of a non-channelopathy gene in mice correlates with the few observations of sudden unexpected death in epilepsy in humans (62). Premature death was observed in Depdc5-Emx1-Cre conditional knockout mice, which is a novel model of Depdc5 deficiency with severe epilepsy and macrocephaly, generated by conditional deletion of Depdc5 in dorsal telencephalic neuroprogenitor cells (40). In these animals, mTORC1 inhibition with rapamycin significantly improved survival and seizures (40).

Differential diagnosis

Sporadic benign focal epilepsies constitute the main clinical differential diagnosis, but unless tested, it is impossible to tell whether these individuals may have mutations and variants in the same gene or genes as patients with familial focal epilepsy with variable foci. It should be noted that some sporadic patients could, in fact, be part of a familial focal epilepsy with variable foci kindred in which the other family members are only mildly affected and sometimes unrecognized. In the case of sporadic French-Canadian patients, however, identification of the same haplotype on ch22q as in the previously reported French-Canadian families constitutes a high probability for a positive diagnosis of familial focal epilepsy with variable foci (79; 78; 15). Finding mutations and variants in GATOR1 complex genes can support the diagnosis of familial focal epilepsy with variable foci, but mutations and variants can also be found in patients without a familial epilepsy syndrome.

Among the genetically determined focal epilepsies, the most important differential diagnosis is ADSHE or sleep-related hyperkinetic/hypermotor seizures because frontal lobe seizures are the most frequent type found in affected family members with familial focal epilepsy, and GATOR1 variants and mutations are frequently associated with sleep-related hyperkinetic seizures of frontal origin. For ADSHE, three loci and two genes have been identified: ENFL1 (chr 20q13.2), with four different mutations and variants in the CHRNA4 gene, coding for the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (AchR); ENFL2 (chr 15q24, gene still unknown); and the CHRNB2 gene on the ENFL3 locus (chr 1q), coding for the beta 2 subunit of the AchR (57; 58; 56; 71; 70; 33; 22; 30; 46). However, most families (88%) with ADSHE do not map to any of these loci and do not have mutations and variants in either the CHRNA4 or CHRNB2 genes. Mutations and variants in the sodium-gated potassium channel gene KCNT1 have also been identified in more severe phenotypes (32).

Aridon and colleagues described a mutation in the CHRNA2 gene associated with nocturnal seizures, fear, and nighttime wandering (03). However, Gu and colleagues did not find mutations and variants in the CHRNA2 gene in 47 families with ADSHE (31). The report of ADSHE kindreds with DEPDC5 or NPRL3 mutations and variants adds to the complexity of the differential diagnosis (60; 41).

In the absence of genetic conformation, the differential diagnosis between familial focal epilepsy with variable foci and ADSHE should be based on the clinical and EEG characteristics of the frontal lobe seizures as well as family history of seizure patterns that indicate foci outside the frontal regions in familial focal epilepsy with variable foci.

The familial temporal lobe epilepsies, both familial mesial temporal lobe epilepsy and familial lateral temporal lobe epilepsy with auditory features should also be considered in the differential diagnosis if one or more affected individuals in the family presents clinical and EEG features of temporal lobe epilepsy. A confirmed extratemporal focus on a family member would exclude the diagnosis of familial mesial temporal lobe epilepsy or familial lateral temporal lobe epilepsy and could suggest familial focal epilepsy with variable foci. Genetic investigation of mutations and variants in the LGI1 gene on chromosome 10q can suggest a possible diagnosis of familial lateral temporal lobe epilepsy (38; 52). LGI1 mutations and variants have been found in about half of the families investigated (14). Mutations and variants in RELN gene on chromosome 7q have been found in 17% of kindreds that tested negative for LGI1 mutations and variants (21; 49). However, the observation of DEPDC5, NPRL2, and NPRL3 mutations and variants in temporal lobe epilepsy probands of mesial and lateral forms further complicates the differential diagnosis based on genetics (61; 72; 16; 63).

An updated review of these familial epilepsy syndromes can be found in the dedicated MedLink clinical summaries for Genetic epilepsy with febrile seizures plus, Epilepsy with auditory features, Familial mesial temporal lobe epilepsy, Hyperkinetic seizures, and Sleep-related hypermotor (hyperkinetic) epilepsy.

Diagnostic workup

A detailed clinical evaluation with clear description of the seizures by the patient and close relatives is the first important requirement for diagnosis of familial focal epilepsy with variable foci, as for any other epilepsy patient.

EEG recordings and, whenever possible, prolonged video-EEG monitoring can help in the definition of the epileptic focus. Interictal epileptiform abnormalities have been recorded in the EEG of 83% of probands, reaching 90% among patients with hypermotor seizures (07).

Structural or functional neuroimaging abnormalities, most often revealing an underlying malformation of cortical development, have been found in 38% of probands. These include focal or hemispheric malformations, with focal cortical dysplasia in approximately 20% of probands, and rarely, hippocampal atrophy. The presence of an MRI lesion suggestive of a malformation of cortical development might lead to the definition of familial epilepsy with focal cortical dysplasia. In contrast, kindreds with solely MRI negative and seizure-free patients have also been described (01).

Genetic testing can now be performed and might show DEPDC5, NPRL2, or NPRL3 mutations and variants. The clinical yield of diagnostic exome sequencing for genetic screening of main genes involved in focal epilepsies is promising (42). In a cohort of 112 patients, 12% showed diagnostic variants, most of which (69%) were GATOR1 genes.

In a study evaluating the yield of whole exome sequencing screening of targeted gene analysis in clinical practice, 40 consecutive patients who had MRI-negative focal epilepsy and a family history of seizures in at least one first- or second-degree relative have been evaluated for 64 epilepsy genes (55). Five (12.5%) patients had a pathogenic (or likely pathogenic) variant in SCN1A, DEPDC5, PCDH19, GABRG2, or NPRL2 genes, and at least in one patient these results determined an important change in the treatment decision, leading to significant improvement of the epilepsy.

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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Eliane Kobayashi MD PhD

Dr. Kobayashi of McGill University received honorariums for advisory board membership from Palladin Laboratories and Jazz Pharmaceuticals.
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Editor

Jerome Engel Jr MD PhD

Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.
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Former Authors

Eva Andermann MD PhD
Frederick Andermann MD

Patient Profile

Age range of presentation: 0 to 65+ years
Sex preponderance: male=female
Heredity: Family history needs to be obtained for diagnosis of this syndrome.
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Localization-related (focal)(partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures: G40.1

Localization-related (focal)(partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures: G40.2
ICD-11: Other specified genetic epileptic syndromes with variable age of onset: 8A61.4Y
OMIM: Familial focal epilepsy with variable foci: #604364

DEPDC5 gene: *614191

NPRL2 gene: *607072

NPRL3 gene: *600928

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Familial focal epilepsy with variable foci

Differential Diagnosis

Sporadic benign focal epilepsies
autosomal dominant sleep-related hyperkinetic/hypermotor epilepsy (ADSHE)
familial mesial temporal lobe epilepsy
epilepsy with auditory features
Familial epilepsy with focal cortical dysplasia

Familial focal epilepsy with variable foci …

Familial focal epilepsy with variable foci

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Alcohol withdrawal seizures

Epileptic lesions due to malformation of cortical development

Epileptic spasms

Sleep and epilepsy

Neocortical temporal lobe seizures

Jacksonian seizures

Familial focal epilepsy with variable foci

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Alcohol withdrawal seizures

Epileptic lesions due to malformation of cortical development

Epileptic spasms

Sleep and epilepsy

Neocortical temporal lobe seizures

Jacksonian seizures

This is an article preview.
Start a Free Account
to access the full version.