Table 3.

Selected Genes of Interest in the Differential Diagnosis of Autosomal Dominant Epilepsy with Auditory Features

Gene(s)DisorderProportion of Disorder Attributed to Pathogenic Variants in Listed GenesClinical Features
Localization of
epileptogenic
zone		Seizure semiologyAge at onsetNeuroimagingEEGOther
CABP4
CHRNA4
CHRNA2
CHRNB2
CRH
DEPDC5
KCNT1
NPRL2
NPRL3
STX1B 		Autosomal dominant sleep-related hypermotor (hyperkinetic) epilepsy (ADSHE)
  • 19% (persons w/family history of SHE)
  • 7% (persons w/negative family history)
Frontal lobe (rarely from extrafrontal areas, e.g., temporal, insular, & parietal regions)Asymmetric tonic/dystonic posturing &/or complex hyperkinetic seizures, mostly during sleep1st 2 decades of life in most persons, typically in adolescenceUsually normal
  • Interictal & ictal scalp EEG features may be normal.
  • Prolonged video EEG recording is best diagnostic test to assess seizure occurrence.
  • Characterized by clusters of nocturnal motor seizures, often stereotyped & brief (5 secs to 5 mins)
  • Clinical neurologic exam normal & intellect usually preserved, but psychiatric comorbidity or cognitive deficits may occur.
  • Manifestations may vary considerably w/in a family.
Unknown
(DEPDC5) 1		Familial mesial temporal lobe epilepsy (FMTLE)Rare 1Mesial temporal lobe 2
  • Psychic symptoms (esp déjà vu) most common
  • Autonomic or special sensory components in ~50%
  • Auditory symptoms in <10%
Usually late adolescence or early adulthoodNormalInterictal epileptiform EEG abnormalities in ~20%
  • Febrile seizure frequency as in general population
  • Benign clinical course, w/long remissions & good response to range of therapies (carbamazepine, phenytoin, or valproate)
Multiple genes incl:
DEPDC5
NPRL2
NPRL3
TSC1
TSC2		Familial focal epilepsy w/variable foci (FFEVF) (OMIM PS604364)Unknown
  • Epileptogenic zone (frontal, temporal, or occipital) differs among family members. 3
  • Frontal lobe seizures most common.
Auditory symptoms & aphasia not described in families w/FPEVF.Usually middle childhood to early adulthoodNormalInterictal & ictal EEG abnormalities localized in different areas (frontal, temporal, occipital)Seizures in FPEVF occur less frequently than in ADNFLE; when they occur, it is more often in daytime.

SHE = sleep-related hypermotor (hyperkinetic) epilepsy

1.

Pathogenic variants in DEPDC5 are a rare cause of FMTLE (see DEPDC5-Related Epilepsy). The molecular basis of FMTLE is unknown in most affected individuals.

2.
3.

From: Autosomal Dominant Epilepsy with Auditory Features

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