Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype.

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(Sadleir L, et. al 2017). Dravet syndrome is often thought to be at the severe end of a spectrum of SCN1A disorders ranging from relatively mild conditions such as migraines to generalized epilepsy with febrile seizures plus (GEFS+) to DS. Even within the “severe” category of DS, patients can present with a wide degree of severity, and mutation type has not been correlated with severity with the exception of truncation mutations being found more often in DS than in milder diagnoses on the SCN1A spectrum. For the first time, this article describes a single SCN1A mutation that appeared in seven out of nine cases of epileptic encephalopathy even more severe than DS.

The authors describe nine unrelated boys aged 3-12 years whose seizures began between 6 and 12 weeks of age, which is significantly earlier than the mean age of 5 months in DS. Astonishingly, seven of the nine boys had the same SCN1A mutation (p.Thr226Met). All children were nonambulatory, had a hyperkinetic movement disorder, and 8 were nonverbal.

The authors distinguish this early infantile SCN1A encephalopathy from Dravet syndrome by the following features: 1. Onset <3 months of age (vs. 4-15 months in DS), 2. Profound developmental impairment (vs. severe to mild intellectual disability in DS), 3. Infantile movement disorders, 4. Epileptic spasms, 5. Tonic seizures in childhood (vs. adulthood in DS). They note that other groups have described single cases of what may be early infantile SCN1A encephalopathy with mutations other than those found in this study.

Jensen MP, Liljenquist KS, Bocell F, Gammaitoni AR, Aron CR, Galer BS, Amtmann D. Life impact of caregiving for severe childhood epilepsy: Results of expert panels and caregiver focus groups. Epilepsy Behav. 2017 Sep;74:135-143. doi: 10.1016/j.yebeh.2017.06.012. Epub 2017 Jul 19. PubMed PMID: 28734197
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