Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline

Dev Med Child Neurol. 2014 Jan;56(1):85-90. doi: 10.1111/dmcn.12322. Epub 2013 Oct 25.

Abstract

Aim: To show that atypical multifocal Dravet syndrome is a recognizable, electroclinical syndrome associated with sodium channel gene (SCN1A) mutations that readily escapes diagnosis owing to later cognitive decline and tonic seizures.

Method: Eight patients underwent electroclinical characterization. SCN1A was sequenced and copy number variations sought by multiplex ligation-dependent probe amplification.

Results: All patients were female (age range at assessment 5-26y) with median seizure onset at 6.5 months (range 4-19mo). The initial seizure was brief in seven and status epilepticus only occurred in one; three were febrile. Focal seizures occurred in four patients and bilateral convulsion in the other four. All patients developed multiple focal seizure types and bilateral convulsions, with seizure clusters in six. The most common focal seizure semiology (six out of eight) comprised unilateral clonic activity. Five also had focal or asymmetric tonic seizures. Rare or transient myoclonic seizures occurred in six individuals, often triggered by specific antiepileptic drugs. Developmental slowing occurred in all: six between 3 years and 8 years, and two around 1 year 6 months. Cognitive outcome varied from severe to mild intellectual disability. Multifocal epileptiform discharges were seen on electroencephalography. Seven out of eight patients had SCN1A mutations.

Interpretation: Atypical, multifocal Dravet syndrome with SCN1A mutations may not be recognized because of later cognitive decline and frequent tonic seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child Development
  • Cognition Disorders / etiology*
  • Cognition Disorders / genetics
  • DNA Copy Number Variations
  • Electroencephalography
  • Epilepsies, Myoclonic / complications*
  • Epilepsies, Myoclonic / diagnosis*
  • Epilepsies, Myoclonic / genetics
  • Epilepsies, Myoclonic / physiopathology
  • Female
  • Humans
  • Intellectual Disability / etiology*
  • Intellectual Disability / genetics
  • Molecular Sequence Data
  • Mutation*
  • NAV1.1 Voltage-Gated Sodium Channel / genetics*
  • Seizures / genetics
  • Seizures / physiopathology

Substances

  • NAV1.1 Voltage-Gated Sodium Channel
  • SCN1A protein, human

Associated data

  • GENBANK/AB093548