Autosomal Dominant Epilepsy with Auditory Features

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. Age at onset is usually in adolescence or early adulthood (age 10-30 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 can be established in a proband with characteristic clinical features, normal brain imaging by MRI, and family history consistent with autosomal dominant inheritance. The molecular diagnosis is established in a proband with characteristic clinical features and a heterozygous pathogenic variant in LGI1, MICAL1, or RELN identified by molecular genetic testing.

Management: Treatment of manifestations: Seizure control is usually readily achieved with standard anti-seizure medications (ASM).

Surveillance: Monitoring of epilepsy as clinically indicated; neurocognitive assessments in individuals suspected to have memory or attention deficits; evaluation by a psychiatrist for any psychiatric comorbidities.

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

Pregnancy management: Discussion of the risks and benefits of using a given ASM during pregnancy should ideally take place prior to conception. Transitioning to a lower-risk medication prior to pregnancy may be possible.

Genetic counseling: By definition, ADEAF is inherited in an autosomal dominant manner. Most individuals diagnosed with ADEAF have an affected parent; the proportion of individuals with ADEAF caused by a de novo pathogenic variant is believed to be low. Offspring of an individual with ADEAF who is heterozygous for a pathogenic variant have a 50% chance of inheriting the pathogenic variant; the chance that offspring who inherit the pathogenic variant will manifest ADEAF ranges from 54% to 85% depending on the assumed penetrance. Once the ADEAF-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.