IllnessEpileptic encephalopathy, early infantile -"Dravet syndrome"; differential diagnosis

NGS +

Dravet syndrome, formerly sometimes called severe myoclonic epilepsy of infancy (SMEI), is an epilepsy syndrome that begins in infancy or early childhood and encompasses a spectrum of symptoms ranging from mild to severe. Initial focal or generalized seizures may begin before 15 months of age. Seizures are often prolonged, may be provoked by temperature changes, and can vary widely in course. Status epilepticus occurs frequently, especially in the first five years of life. Children typically develop normally in the first few years, but as seizures increase, skill acquisition slows and children lag behind their peers in development and show additional nonspecific symptoms. In at least 80%, Dravet syndrome is caused by SCNA1 mutations. Borderline SMEI and generalized epilepsy with febrile seizures plus are caused by defects in the same gene. Dravet syndrome is a lifelong condition; seizures can now be reduced by certain anticonvulsant medications. Although this comprehensive panel covers most monogenic causes of Dravet syndrome, a negative result does not represent a definite exclusion of even very rarely occurring mutations in additional genes.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1318/

Europäische Dravet-Syndrom-(Therapie-)Leitlinie (2022): SCN1A, GABRA1, GABRG2, SCN8A, STXBP1 Gene sind diagnostisch relevant.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.12569

Leitlinie: Diagnostische Prinzipien bei Epilepsien des Kindesalters; S1; From: 18.12.2017, valid until 17.12.2022; Gesellschaft für Neuropädiatrie (GNP): "Zwar haben die neuesten molekulargenetischen Befunde beigetragen, die Ursachen dieser häufigen idiopathischen Epilepsien etwas besser zu verstehen, doch ist eine routinemäßige genetische Diagnostik derzeit noch nicht sinnvoll.." However GRIN2A, KCNT1, KCNQ2, KCNQ3, SCN1A genes explicitly mentioned.

DD: >20 additional genes

• Alias: SMEI, Severe Myoclonic Epilepsy of Infancy
• Allelic: Hydranencephaly with abnormal genitalia (ARX)
• Allelic: Intellectual developmental disorder, XL 29 (ARX)
• Developmental + epileptic encephalopathy 1 (ARX)
• Epilepsy, childhood absence, susceptibility to, 4 (GABRA1)
• Epilepsy, generalized, with febrile seizures plus, type 1 (SCN1B)
• Epilepsy, generalized, with febrile seizures plus, type 2 (SCN1A)
• Epilepsy, generalized, with febrile seizures plus, type 3 (GABRG2)
• Epilepsy, juvenile myoclonic, susceptibility to, 5 (GABRA1)
• Epileptic encephalopathy, early infantile (SCN1B)
• Epileptic encephalopathy, early infantile [EIEE], >68 forms known
• Epileptic encephalopathy, early infantile, 19 (GABRA1)
• Epileptic encephalopathy, early infantile, 4 (STXBP1)
• Epileptic encephalopathy, early infantile, 6 [Dravet syndrome] (SCN1A)
• Epileptic encephalopathy, early infantile, 74 (GABRG2)
• Erythermalgia, primary (SCN9A)
• Febrile seizures, familial, 3A (SCN1A)
• Febrile seizures, familial, 3B (SCN9A)
• Febrile seizures, familial, 8 (GABRG2)
• Generalized epilepsy with febrile seizures plus, type 7 (SCN9A)
• Generalized epilepsy with febrile seizures plus, type 9 (STX1B)
• Insensitivity to pain, congenital (SCN9A)
• Lissencephaly, XL 2 (ARX)
• Migraine, familial hemiplegic (SCN1A)
• Neuropathy, hereditary sensory and autonomic, type IID (SCN9A)
• Paroxysmal extreme pain disorder (SCN9A)
• Partington syndrome (ARX)
• Proud syndrome (ARX)
• Small fiber neuropathy (SCN9A)