Abstracts

Rationale: Rationale: The revised ILAE classification and terminology (Berg et al 2010; Epilepsia 51:676-685) acknowledges that classification of the epilepsies will in future need to incorporate advances being made in basic neurosciences. Benign Familial Neonatal Seizures (BFNS), Benign Familial Neonatal Infantile Seizures (BFNIS) and Benign Familial Infantile Seizures (BFIS) are currently distinguished by ascending mean age of seizure onset (2-3 days; 11 wks; and 6 mths, respectively), but with overlapping distributions (1 day-6 mths; 2 days to 6 mths; and 2 mths to 20 mths, respectively). Families can be skewed in their clinical manifestations, or isolated cases and small families display only a small range of their potential clinical variability, or different mutations in the same gene vary in expressivity due to the specific mutation, or to affects of modifier loci. This can pose a challenge for clinical diagnoses. Methods: Methods: Clinical observation will always direct the most appropriate genetic testing, even when clinical descriptors alone cannot clearly delineate the syndromes. Currently, sequencing of either the potassium channel subunit genes KCNQ2 and KCNQ3 and/or the sodium channel gene SCN2A provides molecular discrimination. Utilisation of laboratory based diagnoses where clinical observations alone are not definitive is compatible with the recent ILAE concept of recognising genetic epilepsies as a distinct classification. Results: Results: Previously BFIS cases have been reported with SCN2A mutations prompting SCN2A to be referred to as both a BFNIS and BFIS gene. In our experience, clinically defined BFNS families have for a time been regarded as having SCN2A mutations prompting SCN2A to also be considered as a BFNS gene, until subsequent investigation of the extended family disclosed wider phenotypic variation consistent with BFNIS. These dilemmas are easily resolved. Patients and families previously diagnosed as BFNS, BFNIS and BFIS could be grouped and renamed Familial Infantile Epilepsy (FIE), since onset for all three is before two years of age and the ILAE now suggest epilepsy be substituted for seizures . FIE could be molecularly refined by addition of a suffix, namely FIE:KCNQ2, FIE:KCNQ3 and FIE:SCN1A if or when genetic test results are available. Benign in the context of these disorders is a misnomer, as we learn more about the course of these conditions, so that disappears. Conclusions: Conclusions: Prognosis and treatment can be based on knowledge of the gene and its mechanism of action. The gene for FIE families mapping to chromosome 16 awaits discovery; hence, these families remain as FIE. Overlaps between clinical entities disappear when molecular criteria are included as part of the diagnostic protocol.