Early-Onset Epileptic Encephalopathies: Ohtahara Syndrome and Early Myoclonic Encephalopathy

Abstract

Ohtahara syndrome and early myoclonic encephalopathy are the earliest presenting of the epileptic encephalopathies. They are typically distinguished from each other according to specific clinical and etiologic criteria. Nonetheless, considerable overlap exists between the two syndromes in terms of clinical presentation, prognosis, and electroencephalographic signature. Newer understandings of underlying etiologies of these conditions may support the previously suggested concept that they represent a single spectrum of disease rather than two distinct disorders. We review both syndromes, with particular focus on the underlying genetics and pathophysiology and implications regarding the classification of these conditions.

Early Myoclonic Encephalopathy in 9q33‐q34 Deletion Encompassing STXBP1 and SPTAN1

“…As well as Ohtahara syndrome, the pathogenesis of EME is variable, with structural, metabolic, and genetic abnormalities all playing a role. However, differently from EESB, focal structural anomalies are less frequently encountered, while associated metabolic diseases, especially nonketotic hyperglycinemia, are more frequently reported (Beal et al, 2012). As for the genetic causes of EME (Pavone et al, 2012), mutation of the ErbB4 and SCL25A22 genes have been recently described (Backx et al, 2009;Cohen et al, 2014), but to the best of our knowledge, the association with STXBP1 and SPTAN1 haploinsufficiency has never been reported.…”

“…In fact, typical EEG characteristics in EME comprises an SB pattern similar to that observed in EESB; however the SB pattern in EME is not continuous and becomes evident during sleep. Finally the SB pattern can evolve into an atypical pattern of hypsarrhythmia in up to 50% of patients (see Table S2) (Beal et al, 2012). Neuroradiological findings of the teen 9q33-q34 deletion patients include thinning of the corpus callosum (66%), cortical atrophy (33%), hypomyelination (22%), cerebellar hypoplasia or Chiari type I malformation (11%).…”

“…Early myoclonic encephalopathy (EME) and early onset epileptic encephalopathy with suppression burst (EESB) are devastating epilepsy syndromes starting in the neonatal or very early infantile period showing considerable clinical overlap (Table S1) (Beal et al, 2012). EME is characterized by early onset of fragmentary and erratic myoclonias and is frequently associated with focal seizures and tonic spasms.…”

Epilepsy genetics: The ongoing revolution

“…The prognosis is usually very poor, with a high mortality rate in infancy or an evolution toward severe ID. In 3 cases out of 4, OS evolves over time into West syndrome, and, more rarely (10%) further evolve into Lennox-Gastaut syndrome [58]. EME is characterized by erratic myoclonus, refractory partial seizures and developmental delay.…”

Two Distinct De novo Pathogenic Sequence Variants in the SCN2A Gene in Children with Early Infantile Epileptic Encephalopathy/Ohtahara Syndrome

“…Early infantile epileptic encephalopathy (EIEE)/Ohtahara syndrome (OS) represents the earliest form of neonatal EEs, because symptoms appear within the three months after delivery, often within 10 days of life [2,3]. Infants acutely develop tonic spasms with variable progression, localization, frequency per day, and with independence of the sleep cycle.…”