• Overview:

    • Temporal lobe epilepsy was traditionally considered an acquired condition.
    • Causes include lesions such as:
      • Hippocampal sclerosis
      • Tumours
      • Trauma
      • Vascular malformations
      • Malformations of cortical development
    • Recent research has highlighted the genetic involvement in some forms of temporal lobe epilepsy.
  • Inheritance:

    • Familial temporal lobe epilepsy is inherited in an autosomal dominant manner.
  • Types:

    • Mesial Familial Temporal Lobe Epilepsy (MFTLE):
      • Characterised by seizure symptomatology typical of mesial temporal lobe epilepsy.
      • Symptoms include:
        • Déjà vu
        • Autonomic phenomena
    • Lateral Familial Temporal Lobe Epilepsy (LFTLE):
      • Also known as partial epilepsy with auditory symptoms.
      • Characterised by subjective ictal symptoms.
      • Symptoms include:
        • Auditory hallucinations originating from the lateral temporal lobe.
  • Onset and Nature:

    • Both MFTLE and LFTLE typically begin in adolescence or adult life.
    • These forms of epilepsy are usually considered benign epilepsy syndromes.

Mesial Familial Temporal Lobe Epilepsy (MFTLE)

  • Overview:

    • MFTLE is an autosomal dominant epileptic disease.
    • Onset typically occurs in teenage or early adult life.
    • Median onset is in the middle of the third decade of life.
    • No cases have been identified in children under 10 years.
    • Women may be affected more than men (58%).
    • Epidemiology is unknown, but it may be a common condition.
  • Clinical Manifestations:

    • Seizures are generally mild, infrequent, and well controlled with antiepileptic drugs (AEDs).
    • Seizure Types:
      • Simple focal seizures (90%) are more common than complex focal seizures (66%).
      • Simple focal seizures may be the only seizure type (18%).
    • Ictal Symptoms:
      • Déjà vu
      • Experiential phenomena and hallucinations
      • Autonomic disturbances
      • Emotional symptoms (fear and panic)
      • Visual and auditory illusions
      • Somatosensory sensations (diffuse numbness and tingling)
    • Generalized Tonic-Clonic Seizures (GTCS):
      • Occur in only two-thirds of patients.
      • In 50% of cases, GTCS occur before appropriate treatment is initiated.
      • Infrequent, with a worst-case scenario of one GTCS per year.
  • Aetiology:

    • Autosomal dominant inheritance with reduced penetrance (60%).
    • The responsible gene has not yet been identified.
  • Diagnostic Procedures:

    • MRI:
      • Often normal but may show hippocampal atrophy in severe cases.
      • Minor, non-specific abnormalities (diffuse, small, high signal areas on T2-weighted images).
    • Interictal FDG-PET:
      • May show ipsilateral temporal hypometabolism in patients with active seizures.
    • EEG:
      • Interictal EEG is usually normal (50% of cases).
      • May show mild, focal, slow waves (28%) or sparse, unilateral sharp and slow wave complexes (22%).
      • Sleep may occasionally activate epileptiform abnormalities.
  • Differential Diagnosis:

    • Differentiating from normal phenomena in cases with mild and infrequent seizures of predominantly déjà vu can be challenging.
    • Main differentiating features from hippocampal epilepsy:
      • Onset in teens or early adult life
      • No febrile convulsions or other antecedent factors
      • No ictal symptoms of rising epigastric aura
      • Mild and infrequent seizures that may remit
      • Usually normal MRI
  • Prognosis:

    • Generally good prognosis.
    • One-sixth of cases with mild simple partial seizures alone might be unaware of their condition if not for affected family members.
    • Complex focal seizures and GTCS are infrequent and respond well to AEDs.
    • Rare for seizures to persist after drug treatment (10-20% of cases).
    • Long remissions, with or without therapy, are common.
    • More severe clinical spectrum observed in patients considering surgical treatment.
  • Management:

    • Seizures are usually easily controlled with carbamazepine or phenytoin.
    • Patients with refractory MFTLE have a good surgical outcome when unilateral or clearly asymmetric hippocampal atrophy is identified.
    • Preoperative investigation should be the same as for patients with sporadic refractory MFTLE.

Lateral Familial (Autosomal Dominant) Temporal Lobe Epilepsy (LFTLE)

  • Overview:

    • Also known as "autosomal dominant focal epilepsy with auditory features."
    • Caused by defects in the same gene.
    • First non-ion channel familial epilepsy discovered.
    • Previously discovered genes for idiopathic epilepsies were associated with ion channels.
  • Demographic Data:

    • Onset typically in teenage or early adult life.
    • Can occur as early as 5-10 years of age or later.
  • Clinical Manifestations:

    • Seizure Characteristics:
      • Mild seizures with mainly auditory hallucinations.
      • Mainly nocturnal and infrequent generalized tonic-clonic seizures (GTCS).
      • Excellent response to treatment with antiepileptic drugs (AEDs).
    • Seizure Types:
      • Simple focal seizures are most common.
        • Auditory hallucinations (ringing, humming, clicking, unspecified noises).
        • Other sensory symptoms (visual, olfactory, vertiginous, cephalic).
      • Autonomic, experiential, and motor symptoms are less common.
      • Simple focal seizures may progress to complex focal seizures.
      • Brief aphasic seizures have been described.
    • GTCS:
      • Rare and predominantly nocturnal.
  • Aetiology:

    • Autosomal dominant inheritance with high penetrance (~80%).
    • Linked to chromosome 10q, localizing a gene in a common overlapping region of 3-cM at 10q24 (LGI1/Epitempin gene).
    • LGI1 mutations cause protein truncation, leading to loss of function.
    • LFTLE is genetically heterogeneous; LGI2, LGI3, or LGI4 mutations do not account for all cases.
  • Diagnostic Procedures:

    • EEG and MRI are often normal or show mild, non-specific abnormalities.
    • Interictal EEG epileptiform abnormalities are rare.
  • Prognosis:

    • Excellent prognosis.
    • Patients are neurologically and mentally normal.
    • The condition does not significantly affect normal life, especially with medication.
  • Differential Diagnosis:

    • Differentiated from other structural causes of lateral temporal lobe epilepsy.
    • Different from hippocampal and other types of mesial familial temporal lobe epilepsy (MFTLE).
      • Main ictal symptom of LFTLE: auditory hallucinations.
      • Main ictal symptoms of MFTLE: déjà vu and other experiential phenomena.
  • Management:

    • Excellent response to carbamazepine.

Familial Focal Epilepsy with Variable Foci

  • Overview:

    • Familial partial epilepsy with variable foci is an autosomal dominant syndrome.
    • Characterized by focal seizures originating from different brain regions in different family members.
    • Occurs in the absence of detectable structural abnormalities.
  • Demographic Data:

    • Age at onset varies widely (from months to 43 years).
    • Mean age at onset of seizures is 13 years.
    • Reported in eight unrelated families to date.
  • Clinical Manifestations:

    • Different family members have focal seizures from different cortical locations:
      • Temporal
      • Frontal
      • Centroparietal
      • Occipital
    • Each patient has a consistent electroclinical pattern of single-location focal epilepsy.
    • Seizures are often nocturnal.
    • Great intrafamilial variability in severity:
      • Some are asymptomatic with only an EEG spike-focus.
      • Most are easily controlled with AEDs.
      • A few may be intractable to medication.
    • Identification is challenging in small families due to insufficient individuals to establish a specific pattern.
  • Aetiology:

    • Rare inherited syndrome with autosomal dominant inheritance.
    • Penetrance of about 60%.
    • In two families, mapped to a locus on chromosome 22q11-q12.
    • Genetic heterogeneity indicated by non-linkage to chromosome 22 in the original Australian family and a suggestion of linkage on chromosome 2q.
  • Diagnostic Procedures:

    • Neuroimaging:
      • Usually normal.
    • Electroencephalography (EEG):
      • Interictal focal epileptiform abnormalities occur in most patients.
      • Locations vary between family members but remain constant for each individual over time.
      • Abnormalities often facilitated or brought on by sleep.
      • Clinical seizures align with EEG localization.
      • EEG severity varies among individuals and does not correlate with seizure frequency.
      • Normal family members may also exhibit an EEG spike focus, indicating it as a marker for the syndrome.
  • Prognosis:

    • Development is usually normal.
  • Management:

    • Effects of new AEDs not directly evaluated.
    • Carbamazepine and phenytoin appear to be effective.

Autosomal Dominant Rolandic Epilepsy and Speech Dyspraxia

  • Overview:

    • Described as a rare hereditary condition by the Australian team of Berkovic, Scheffer, and associates.
    • Characterized by nocturnal oro-facio-brachial focal seizures, secondarily generalized tonic-clonic seizures (GTCS), and centrotemporal epileptiform discharges.
    • Associated with oral and speech dyspraxia and cognitive impairment.
    • The speech disorder differs from that in Landau-Kleffner syndrome and epilepsy with continuous spike and wave during slow-wave sleep.
  • Demographic Data:

    • Studied in a family of nine affected individuals across three generations.
    • Patients in previous generations were less severely affected but also had neurological deficits, mainly oral and speech dyspraxia without evidence of dysarthria.
  • Clinical Manifestations:

    • Seizure Characteristics:
      • Nocturnal oro-facio-brachial focal seizures.
      • Secondarily generalized tonic-clonic seizures (GTCS).
      • Centrotemporal epileptiform discharges.
    • Neurological Deficits:
      • Prominent oral and speech dyspraxia.
      • Cognitive impairment.
      • In some cases, neurological deficits precede seizures.
  • Aetiology:

    • Autosomal dominant inheritance.
    • Clinical anticipation observed in seizure disorder, oral and speech dyspraxia, and cognitive dysfunction.
    • Genetic mechanism could involve expansion of an unstable triplet repeat.
  • Prognosis:

    • The condition shows clinical anticipation, meaning symptoms may worsen or appear earlier in successive generations.
    • Permanent neurological deficits make it distinct from benign rolandic epilepsy.
  • Clinical Significance:

    • Resembles benign rolandic epilepsy in some electroclinical features but differs due to permanent neurological deficits and anticipation.
    • Molecular studies on this syndrome may help identify a gene for benign rolandic epilepsy, where anticipation does not occur and the mode of inheritance is uncertain.
  • Management:

    • Specific management strategies not detailed; implications for treatment and genetic counseling need further research.

Focal Epilepsy with Pericentral Spikes

  • Overview:

    • Based on the study of a family with a variety of seizure types.
    • Seizure types include hemiclonic, hemitonic, generalized tonic-clonic seizures (GTCS), simple focal (stereotyped episodes of epigastric pain), and complex focal seizures with temporal lobe semiology.
    • The syndrome is benign, requiring no treatment or responding well to a single antiepileptic drug (AED).
  • Demographic Data:

    • Seizure onset typically occurs in the first or second decades of life.
    • Seizures can persist up to 71 years of age.
    • EEG changes have been documented up to the age of 30 years.
  • Clinical Manifestations:

    • Seizure Types:
      • Hemiclonic
      • Hemitonic
      • Generalized tonic-clonic seizures (GTCS)
      • Simple focal seizures (stereotyped episodes of epigastric pain)
      • Complex focal seizures consistent with temporal lobe semiology
    • EEG Abnormalities:
      • Characteristic spikes or sharp waves in the pericentral region:
        • Centroparietal
        • Centrofrontal
        • Centrotemporal
    • Variability:
      • The syndrome may be overlooked due to variability in penetrance and seizure types among affected family members.
  • Aetiology:

    • Evidence for linkage to chromosome 4p15.
  • Prognosis:

    • The syndrome is benign.
    • Seizures are either self-limiting or respond well to a single AED.
  • Management:

    • Treatment is often not required.
    • When needed, seizures respond well to a single AED.

Cite this: ICNApedia contributors.Familial (Autosomal Dominant) Focal Epilepsies. ICNApedia, The Child Neurology Knowledge Environment. 09 November 2024. Available at: https://icnapedia.org/knowledgebase/articles/familial-autosomal-dominant-focal-epilepsies Accessed  09 November 2024. 

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