Childhood absence epilepsy (CAE), also known as
pyknolepsy, is an
idiopathic generalized epilepsy which occurs in otherwise normal children. The age of onset is between 4-10 years with peak age between 5-7 years. Children have
absence seizures which although brief (~4-20 seconds), they occur frequently, sometimes in the hundreds per day. The
absence seizures of CAE involve abrupt and severe impairment of consciousness. Mild
automatisms are frequent, but major motor involvement early in the course excludes this diagnosis. The EEG demonstrates characteristic "typical 3Hz spike-wave" discharges. Prognosis is excellent in well-defined cases of CAE with most patients "growing out" of their epilepsy
[1]CAE is a complex polygenic disorder. Particularly in the Han Chinese population there is association between mutations in CACNA1H and CAE. These mutations cause increased channel activity and associated increased neuronal excitability. Seizures are believed to originate in the thalamus, where there is an abundance of T-type calcium channels such as those encoded by CACNA1H.
There are currently 20 mutations in CACNA1H associated with CAE. These mutations are likely not wholly causative and should instead be thought of as giving susceptibility. This is particularly true since some groups have found no connection between CAE and CACNA1H mutations.[2] Many of the CACNA1H mutations have a measurable effect on channel kinetics, including activation time constant and voltage dependence, deactivation time constant, and inactivation time constant and voltage dependence (summarized in Table 1). Many of these mutations should lead to neuronal excitability, though others may lead to hypoexcitability. These predictions are due to mathematical modeling and may differ from what will occur in real neurons where other proteins, some of which may interact with CACNA1H, are present.
Along with mutations in CACNA1H, two mutations in the gene encoding a GABAA receptor ? subunit are also associated with a CAE like phenotype that also overlaps with generalized epilepsy with febrile seizures plus type-3. The first of these, R43Q, abolishes benzodiazepine potentiation of GABA induced currents.[3][4] The second associated mutation, C588T has not been further characterized.
