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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Neurology

Biology, Genetics, and Diagnosis

At a Glance

Epilepsy with auditory features can be difficult to confirm because routine MRI and EEG may be normal. Doctors may combine the episode history with prolonged video-EEG, sleep-deprived EEG, 3-T MRI, and genetic testing; a negative panel does not exclude the condition.

Epilepsy with Auditory Features (EAF) is a neurological condition where the “wiring” in the brain’s sound-processing center—the lateral temporal lobe—is overly excitable [1][2]. In an important subset of familial cases, this is due to a small change in a single gene that controls how brain cells communicate [3].

The Role of Genetics: LGI1 and RELN

While EAF can happen to anyone and is often sporadic, about 50% of families with the inherited form (called ADLTE) have a mutation in the LGI1 gene [4][3]. This gene provides instructions for a protein that acts like a “brake” on the brain’s electrical signals [5]. When the LGI1 protein doesn’t work correctly, the brain cells in the temporal lobe become hyperactive, leading to auditory seizures [3].

Other important genes include:

  • RELN: About 17.5% of families in selected cohorts have mutations in this gene, which helps brain cells migrate and stabilize their connections [6][7].
  • MICAL1: A rarer cause (found in about 7% of families in some cohorts) that affects the internal structure of brain cells [8][9].
  • DEPDC5: A gene involved in a growth-regulating pathway called mTOR; it is a known cause of various focal epilepsies, including some EAF cases [10][11].

Understanding “Reduced Penetrance”

Familial EAF is typically inherited in an autosomal dominant pattern, meaning you only need one copy of the mutated gene from one parent to potentially have the condition [8]. However, it has reduced penetrance, often estimated at roughly 70% in certain families [8]. This means that out of 10 people who carry the gene, only about 7 will ever actually have a seizure [8]. This is why a family history can sometimes look “empty” even when the gene is present—some relatives carry the gene but never experience symptoms [12]. (Note: Genetic counseling is highly recommended before testing. Relatives shouldn’t be screened just because you have EAF; it is directed by a confirmed variant.)

Why Standard Tests Often Fail

One of the most frustrating parts of the patient journey is receiving “normal” test results while still having symptoms. EAF is notoriously difficult to catch on standard tests for two reasons:

  1. The “Normal” MRI: In many cases of EAF, there is no visible tumor, scar, or malformation in the brain [13]. Because the problem is at the microscopic, chemical level of the brain cells, a standard MRI (Magnetic Resonance Imaging) often appears completely healthy [14].
  2. The “Normal” EEG: A routine EEG (electroencephalogram) only records the brain’s electrical activity for about 20–30 minutes [15]. While interictal (between-seizure) epileptiform discharges can occur, the EEG often misses the “spike” activity because of limited sensitivity. Even in some confirmed cases, the scalp EEG remains unremarkable [16].

Advanced Diagnostic Tools

To confirm a diagnosis and rule out other conditions (like psychogenic non-epileptic seizures, schizophrenia, or tinnitus), doctors use more intensive tools [17][2]:

  • 3-T MRI: This is a higher-resolution scan that can sometimes pick up very subtle changes in the temporal lobe that standard 1.5-T scans miss [18][19]. (However, even a 3-T MRI can be normal.)
  • Prolonged Video-EEG: By recording the brain for several days, doctors are more likely to capture a “habitual event” (a typical seizure) and see where the electrical activity starts [20][15].
  • Sleep-Deprived EEG: Lack of sleep can sometimes trigger the abnormal electrical activity, making it easier to see on an EEG [21].
  • Genetic Testing: A blood or saliva test can confirm if you carry an LGI1, RELN, or other associated mutation, providing strong supporting evidence [10]. (Keep in mind a negative panel does not rule out EAF, and an “uncertain” variant is not diagnostic.)

Ruling Out Other Conditions

The diagnostic process must be careful to distinguish EAF from differential diagnoses—other conditions that look similar:

  • Inner-Ear Issues: Persistent vertigo or hearing loss usually suggests an ear problem, whereas EAF symptoms are brief and episodic [2].
  • Psychiatric Issues: Psychiatric hallucinations can have overlaps with brief seizure-related “beeps” or “buzzes”, but an expert clinician synthesizes history and video-EEG to differentiate them [2].
  • Syncope: “Fainting spells” can sometimes look like seizures, and doctors may check your heart rhythm during an EEG to be sure [22].

Common questions in this guide

Can epilepsy with auditory features occur if my MRI and routine EEG are normal?
Yes. Many people with epilepsy with auditory features have no visible structural abnormality on MRI, and a 20- to 30-minute routine EEG can miss intermittent seizure activity. Prolonged video-EEG, sleep-deprived EEG, or a higher-resolution 3-T MRI may provide additional information, but normal results do not by themselves exclude the condition.
Which genes are linked to epilepsy with auditory features?
LGI1 is a commonly identified gene in inherited epilepsy with auditory features, while RELN, MICAL1, and DEPDC5 are additional genes associated with some families. A relevant finding can support the diagnosis, but a negative genetic panel does not rule out the condition, and a variant of uncertain significance is not diagnostic.
What does reduced penetrance mean in familial epilepsy with auditory features?
Reduced penetrance means that a person can carry an associated genetic variant without ever having a seizure. In some families, about 7 out of 10 carriers develop seizures, but the actual likelihood varies, so genetic counseling is important.
Can I have epilepsy with auditory features without a family history of seizures?
Yes. The condition can occur sporadically, and a family history may appear absent when relatives carry a variant but never develop seizures. A neurologist or genetic counselor can discuss whether a newly occurring genetic variant or another cause should be considered.
What tests help doctors diagnose epilepsy with auditory features?
Doctors may combine a detailed description of the episodes with 3-T MRI, prolonged video-EEG, sleep-deprived EEG, and genetic testing. These tests can help capture a typical event, identify abnormal electrical activity, detect subtle brain changes, or find an associated gene variant.
Should my relatives have genetic testing if I have epilepsy with auditory features?
Relatives generally should not be screened solely because one family member has the condition. Testing is usually guided by a confirmed genetic variant and should be discussed with a genetic counselor, who can explain what the result could mean for each relative.

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my 3-T MRI show any subtle 'gray-white matter blurring' or other features in the temporal lobes?
  2. 2.If my routine EEG was normal, should we proceed to a sleep-deprived EEG or a multi-day video-EEG to capture my symptoms?
  3. 3.Since I have no family history of seizures, could my symptoms still be caused by a 'de novo' mutation in a gene like LGI1 or RELN?
  4. 4.Can you explain the genetic testing panel you are ordering? Does it include MICAL1 and DEPDC5?
  5. 5.How do we definitively rule out non-epileptic causes like psychogenic events or an inner-ear disorder in my case?

References

References (22)
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    Epilepsy With Auditory Features: From Etiology to Treatment.

    Furia A, Licchetta L, Muccioli L, et al.

    Frontiers in neurology 2021; (12()):807939 doi:10.3389/fneur.2021.807939.

    PMID: 35153984
  2. 2

    Ictal aphasia in LGI1-related autosomal dominant epilepsy with auditory features.

    Moloney PB, McHugh J, O'Byrne J, et al.

    Practical neurology 2022; (22(4)):317-320 doi:10.1136/practneurol-2022-003366.

    PMID: 35354661
  3. 3

    Biallelic LGI1 and ADAM23 variants cause hippocampal epileptic encephalopathy via the LGI1-ADAM22/23 pathway.

    Hirano Y, Miyazaki Y, Ishikawa D, et al.

    Brain : a journal of neurology 2025; (148(10)):3514-3522 doi:10.1093/brain/awaf202.

    PMID: 40455867
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    Screening LGI1 in a cohort of 26 lateral temporal lobe epilepsy patients with auditory aura from Turkey detects a novel de novo mutation.

    Kesim YF, Uzun GA, Yucesan E, et al.

    Epilepsy research 2016; (120()):73-8.

    PMID: 26773249
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    Secretion-Positive LGI1 Mutations Linked to Lateral Temporal Epilepsy Impair Binding to ADAM22 and ADAM23 Receptors.

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    PLoS genetics 2016; (12(10)):e1006376 doi:10.1371/journal.pgen.1006376.

    PMID: 27760137
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    The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations.

    Michelucci R, Pulitano P, Di Bonaventura C, et al.

    Epilepsy & behavior : E&B 2017; (68()):103-107 doi:10.1016/j.yebeh.2016.12.003.

    PMID: 28142128
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    Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy.

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    PMID: 26046367
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    A de novo pathogenic variant in MICAL-1 causes epilepsy with auditory features.

    Bonanni P, Giorda R, Michelucci R, et al.

    Epilepsia open 2024; (9(3)):1083-1087 doi:10.1002/epi4.12937.

    PMID: 38654463
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    Mutations in MICAL-1cause autosomal-dominant lateral temporal epilepsy.

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    Annals of neurology 2018; (83(3)):483-493 doi:10.1002/ana.25167.

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    Epilepsy with auditory features: Contribution of known genes in 112 patients.

    Bisulli F, Rinaldi C, Pippucci T, et al.

    Seizure 2021; (85()):115-118 doi:10.1016/j.seizure.2020.12.015.

    PMID: 33453592
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    DEPDC5-related epilepsy: A comprehensive review.

    Samanta D

    Epilepsy & behavior : E&B 2022; (130()):108678 doi:10.1016/j.yebeh.2022.108678.

    PMID: 35429726
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    Whole Exome Sequencing Identifies Novel Homozygous LGI1 Variant Mimicking ADAM22-Related Pathologies in a Moroccan Family.

    El Mouhi H, Elmakhzen B, Bouyahyaoui A, et al.

    BMJ neurology open 2025; (7(2)):e001267 doi:10.1136/bmjno-2025-001267.

    PMID: 41000458
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    CNTNAP2 mutations and autosomal dominant epilepsy with auditory features.

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    Epilepsy research 2018; (139()):51-53 doi:10.1016/j.eplepsyres.2017.11.006.

    PMID: 29179159
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    Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia.

    Klein KM, Pendziwiat M, Cohen R, et al.

    Journal of neurology 2016; (263(1)):11-6 doi:10.1007/s00415-015-7921-2.

    PMID: 26459092
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    Instruction manual for the ILAE 2017 operational classification of seizure types.

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    Molecular typing of familial temporal lobe epilepsy.

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    Autosomal dominant lateral temporal lobe epilepsy associated with a novel reelin mutation.

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This page explains the genetics and diagnostic tests for epilepsy with auditory features for informational purposes only and does not constitute medical advice. A neurologist or genetic counselor should interpret your symptoms and test results.