(Cetica, 2017). Now that genetic testing is becoming more common and less expensive, more infants under 12 months are being tested for SCN1A mutations. For infants who are positive for SCN1A mutations, the question of how those mutations will present clinically remains to be answered at such a young age. In this study of medical records, published in Neurology, the authors analyzed 200 Italian patients with SCN1A mutations, 182 of whom had seizures, and found that just under half (48.5%) had Dravet syndrome, 23.8% had GEFS+, 14.8% had febrile seizures, 3.5% had focal epilepsy, and 8.9% were healthy relatives. Statistical analysis showed that 85% of those who had an SCN1A mutation and their first seizure between 0 and 6 months went on to develop Dravet syndrome, compared to 51% of those whose first seizure was between 6 and 12 months and 0% whose first seizure was after 12 months. The mean age at seizure onset was 5.9 months for those with Dravet syndrome (most commonly in the 6th month) and 18.4 months for those without Dravet syndrome. Although truncation (or nonsense) mutations were more common in patients with Dravet syndrome than non-Dravet (40% vs. 13%), the age at seizure onset was a far more predictive factor for clinical outcome than mutation type. The authors completed an in-depth mutational analysis that supports previous studies of the variability between genotype (the mutation) and phenotype (clinical appearance). The authors conclude that infants with seizures that begin under 1 year of age, particularly if prolonged, should be tested for SCN1A mutations and treated with medication typically used in Dravet syndrome such as clobazam and stiripentol, before the epileptic encephalopathy is established.

Cetica V, Chiari S, Mei D, Parrini E, Grisotto L, Marini C, Pucatti D, Ferrari A, Sicca F, Specchio N, Trivisano M, Battaglia D, Contaldo I, Zamponi N, Petrelli C, Granata T, Ragona F, Avanzini G, Guerrini R. Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations. Neurology. 2017 Feb 15. pii: 10.1212/WNL.0000000000003716. doi: 10.1212/WNL.0000000000003716. [Epub ahead of print] PubMed PMID: 28202706. http://www.neurology.org/content/early/2017/02/15/WNL.0000000000003716