Autosomal Dominant Epilepsy with Auditory Features

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].

Excerpt

Clinical characteristics: Autosomal dominant epilepsy with auditory features (ADEAF) is a focal epilepsy syndrome with auditory symptoms and/or receptive aphasia as prominent ictal manifestations. The most common auditory symptoms are simple unformed sounds including humming, buzzing, or ringing; less common forms are distortions (e.g., volume changes) or complex sounds (e.g., specific songs or voices). Ictal receptive aphasia consists of a sudden onset of inability to understand language in the absence of general confusion. Less commonly, other ictal symptoms may occur, including sensory symptoms (visual, olfactory, vertiginous, or cephalic) or motor, psychic, and autonomic symptoms. Most affected individuals have focal to bilateral tonic-clonic seizures, usually accompanied by "focal aware" and "focal impaired-awareness" seizures, with auditory symptoms as a major focal aware seizure manifestation. Some persons have seizures precipitated by sounds such as a ringing telephone. Age at onset is usually in adolescence or early adulthood (range: age 4-50 years). The clinical course of ADEAF is benign. Seizures are usually well controlled after initiation of medical therapy.

Diagnosis/testing: The clinical diagnosis of ADEAF is established in a proband with characteristic clinical features, normal brain imaging (MRI or CT), and family history consistent with autosomal dominant inheritance. Identification of a heterozygous pathogenic variant in LGI1, MICAL1, or RELN by molecular genetic testing establishes the diagnosis if other findings are inconclusive.

Management: Treatment of manifestations: Seizure control is usually readily achieved with anti-seizure medication used routinely in clinical practice (including but not limited to carbamazepine, phenytoin, valproate, and levetiracetam).

Evaluation of relatives at risk: Interviewing relatives at risk to identify those with suggestive findings may enable early treatment in those who develop seizures.

Genetic counseling: ADEAF is inherited in an autosomal dominant manner. Most individuals with ADEAF have an affected parent; the proportion of cases caused by a de novo pathogenic variant is believed to be very low. Each child of an individual with ADEAF has a 50% chance of inheriting the pathogenic variant. The chance that the offspring who inherits the pathogenic variant will manifest ADEAF is between 55% and 78%, depending on the penetrance. While prenatal diagnosis for pregnancies at increased risk and preimplantation genetic testing are possible if the pathogenic variant in the family is known, prenatal testing and preimplantation genetic testing are rarely requested for conditions that (like ADEAF) do not affect intellect and are usually easily treated.

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  • Review