Some of these are summarized in Table 15-3, and their number will almost certainly expand in the next few years. As with numerous other genetic neurologic disorders, a single mutation may produce different epilepsy and seizure types, and a single type may be the result of one of several different mutations. Also notable is the low penetrance of some monogenic epileptic disorders, particularly the autosomal dominant one associated with nocturnal frontal seizures.
Another group of epilepsies with mendelian inheritance has been ascribed to genetic defects that do not implicate ion channels. Most of these are primarily myoclonic disorders in which the epilepsy is one component. Two forms of progressive myoclonic epilepsy, Unverricht-Lundborg disease and Lafora body disease, are the result, respectively, of mutations in genes encoding cystatin B and tyrosine phosphatase. To these inherited forms of epilepsy may be added diseases such as tuberous sclerosis and ceroid lipofuscinosis (Chap. 36), which have a strong proclivity to cause seizures and genetically determined heterotopias such as FLN1 (this and other developmental aberrations are discussed in Chap. 37).
More complex genetic elements are identified in several childhood seizure disorders—absence epilepsy with 3-per-second spike-and-wave discharges and benign epilepsy of childhood with centrotemporal spikes—both of which are transmitted as autosomal dominant traits with incomplete penetrance or perhaps in a more complicated manner. In the partial, or focal, epilepsies the role of heredity is not nearly so clear. Yet in numerous studies there has been a greater-than-expected incidence of seizures, EEG abnormalities, or both among first-degree relatives. Among the familial cortical epilepsies, both a temporal and frontal lobe type, are inherited in a polygenic fashion or in an autosomal dominant pattern. Undoubtedly also inherited, is the tendency to develop simple febrile convulsions, though the mode of inheritance is uncertain. Finally, copy number variations probably play a role in approximately 5 percent of cases according to Olsen and colleagues.
The physician faced with a patient who seeks advice about an episodic disorder of nervous function must determine first, whether the episode in question is a seizure. In the diagnosis of epilepsy, history is the key; in many adult cases the physical examination is unrevealing. The examination in infants and children is of greater value, as the finding of dysmorphic and cutaneous abnormalities allow the diagnosis of a number of highly characteristic cerebral diseases that give rise to epilepsy.
Paramount in establishing that there has been a seizure is a description from a witness. A detailed account of the event is required and in particular, the type and duration of bodily movements, level of alertness and responsiveness during and immediately after the episode, skin color and breathing, and incontinence. If a witness is not available, then a telephone call to observers and family may give more information than does sophisticated laboratory testing. From the patient, information can be obtained regarding tongue biting, incontinence, and recollection of the event of the immediately preceding epoch. If the patient is able to provide information, previous events that may have been misinterpreted as other than a seizure, for example, brief losses of consciousness, myoclonic jerks, rumpled bedsheets with incontinence, unexplained falls with injury and so forth, may hint at preceding seizures. The family history, developmental milestones, neonatal events and the circumstances of birth are useful additional aspects of the evaluation of epilepsy.