This article includes discussion of benign infantile seizures and benign familial and nonfamilial infantile seizures. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Benign familial and nonfamilial infantile seizures are 2 entities included in the last Classification of Epilepsies and Epileptic Syndromes. The familial form has an autosomal dominant inheritance. In this article, the authors present the clinical, neurophysiological, and genetic data of these 2 entities, which have overlapping characteristics. Recent data support the hypothesis that this disease is linked to alteration of a synaptic protein, PRRT2, in most familial cases, even though ion channel-encoding mutations are involved in some families (KCNQ2, KCNQ3, SCNA2, and SCNA8).
Historical note and terminology
The 1989 classification of epilepsies and epileptic syndromes of the International League Against Epilepsy (ILAE) includes familial and nonfamilial neonatal convulsions as well as benign myoclonic epilepsy among the idiopathic forms with onset during the first year of life. Idiopathic etiology and benign outcome of other epileptic syndromes with onset during the same period are also now recognized (Anonymous 1989).
In 1963 Fukuyama reported cases occurring in the first 2 years of life that were characterized by focal seizures, absence of etiologic factors, and benign outcome (Fukuyama 1963). Later, other reports described the localization and semiology of seizures (Watanabe et al 1987; Watanabe et al 1990; Watanabe et al 1993), prognosis (Sugiura et al 1983), and presence or absence of familial occurrence (Vigevano et al 1990; Vigevano et al 1992; Vigevano et al 1994).
In particular, on several occasions, Watanabe and coworkers described partial epilepsy of infancy with complex partial seizures and benign partial epilepsy with secondarily generalized seizures in infancy. Most of these cases were not familial.
During approximately the same period, Vigevano and coworkers focused their attention on cases that exhibited a family history of convulsions with benign outcome during infancy and autosomal dominant inheritance, suggesting the term "benign infantile familial convulsions.” In 2001, the ILAE Task Force on Classification and terminology stated that the term "seizure" is preferred to the term "convulsion" (Engel 2001), and this has been confirmed more recently by Berg and colleagues (Berg et al 2010). Benign infantile seizures are also now divided into familial and nonfamilial forms (Engel 2001). These 2 forms may, however, have features that overlap (Lispi et al 2001; Caraballo et al 2003). In the 2010 report of the ILAE Commission on Classification and Terminology (Berg et al 2010), benign infantile epilepsy and benign familial infantile epilepsy have been identified and classified among the electroclinical syndromes of infancy.
Early genetic studies in familial forms led to the identification of a linkage to chromosome 19 q12-q13.11 (Guipponi et al 1997). This was not confirmed by later studies, however, and genetic heterogeneity was hypothesized (Gennaro et al 1999). In 1997 Szepetowski described the association between benign infantile familial convulsions and variably expressed paroxysmal choreoathetosis (Szepetowski et al 1997). The identification of a specific marker on chromosome 16p12-q12 constituted a variant of the familial forms, called "infantile convulsions and choreoathetosis." Since then, such specificity of chromosome linkage has not been maintained; in 2001 Caraballo and colleagues found a linkage of pure benign infantile familial convulsions to chromosome 16 in the infantile convulsions and choreoathetosis region, suggesting that this is a major genetic locus underlying both benign infantile familial convulsions and paroxysmal choreoathetosis (Caraballo et al 2001). Similar data were obtained by Weber and colleagues in 14 families with benign familial infantile seizures without paroxysmal choreoathetosis (Weber et al 2004). Afterwards, performing an analysis on 16 families, Striano and colleagues further confirmed the relevance of linkage with chromosome 16 in some families of patients affected by benign familial infantile seizures, as well as the genetic heterogeneity of this syndrome (Striano et al 2006b).
Finally, in the last few years it has been shown that a mutation in the PRRT2 gene, which is located on chromosome 16p12-q12, is present in approximately 80% of families with benign familial infantile seizures and infantile convulsions and choreoathetosis (Lee et al 2011; Heron et al 2012). To date, the mechanisms by which the mutation of the PRRT2 gene is related to the occurrence of seizures for a short period of time in benign familial infantile seizures families are completely unknown. There are reports of sporadic cases of benign infantile convulsions associated with prolonged episodes of diarrhea caused by rotavirus infections (Contino et al 1994). However, clear cause-effect relation is still to be demonstrated.
The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.
If you are a subscriber, please log in.
If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.