Epileptic encephalopathy with continuous spikewaves in slow sleep the combination of various kinds of cognitive deterioration with high. Readers of beyond the ion channel will know that we often post about scn1a, one of the first discovered and most common genetic causes of epileptic encephalopathy. The followup cohorts included 95 additional individuals 41 male and 54 female with feversensitive epileptic encephalopathy referred for early genetic testing of dravet syndrome and 62 individuals with refractory epileptic encephalopathy and seizure onset within the first 4. The seizures in scn8arelated epilepsy with encephalopathy include involuntary muscle contractions that occur before age 1 infantile spasms, partial. This study aimed to broaden the phenotypicspectrum of disease related with scn8a mutations. Dec 31, 2012 epileptic encephalopathy can complicate many different epileptic conditions. The code is valid for the year 2020 for the submission of hipaacovered transactions. Stxbp1 mutations in early infantile epileptic encephalopathy with suppressionburst pattern. Oct 26, 2016 early infantile epileptic encephalopathy eiee is a neurological disorder characterized by seizures. Complete loss of kcna1 activity causes neonatal epileptic. Scn8arelated epilepsy with encephalopathy is a condition characterized by recurrent seizures epilepsy, abnormal brain function encephalopathy, and intellectual disability. A longer polyalanine expansion mutation in the arx gene causes early infantile epileptic encephalopathy with suppressionburst pattern ohtahara syndrome.
Early infantile epileptic encephalopathy eiee is a devastating epilepsy syndrome with onset in the first months of life. Later in 2010, researchers defined epileptic encephalopathy as a condition where the epileptic activity itself may contribute to severe cognitive and behavioral impairments above and beyond what. These syndromes include early myoclonic encephalopathy and ohtahara syndrome in the neonatal period, west. A diagnostic scheme for people with epileptic seizures and with epilepsy proposed by ilae commission 2001 engel, jr. Lossoffunction mutations in udpglucose 6dehydrogenase. The signs and symptoms of this condition typically begin in infancy. Roger j, bureau m, dravet c, dreifuss f, perret a and wolf p eds. Epileptic encephalopathy with continuous spikeandwave during sleep.
Early infantile epileptic encephalopathy eiee early infantile epileptic encephalopathy with suppressionburst ohtahara syndrome. Mutation in the scn2a gene can also cause benign familial infantile seizures3 bfis3. To identify the pathogenic gene of a chinese family, in which six members suffered from epilepsy, wholeexome sequencing was performed. The disorder affects newborns, usually within the first three months of life most often within the first 10 days in the form of epileptic seizures. Early infantile epileptic encephalopathy genetic and. The article provides a phenotypic summary of 147 patients with stxbp1e pathogenic variants, including 45 previously unreported patients with 33 novel stxbp1. Dec 20, 2001 epileptic encephalopathy with continuous spikewaves in slow sleep the combination of various kinds of cognitive deterioration with high. Epileptic and epileptiform encephalopathies treatment.
To advance the understanding of kcnq2 encephalopathy genotypephenotype relationships and to begin to assess the potential of selective kcnq channel openers as targeted treatments. Appropriate differential diagnosis of epileptic seizures as well as subclinical. The onset of this epileptic encephalopathy is between 2 months and 12 years of age with a peak at 47 years of age. Molecular pathology caused by defects of stxbp1, which encodes a syntaxinbinding protein. Definition diagnostic criteria early infantile epileptic encephalopathy eiee or ohtahara syndrome is the earliest form of agedependent encephalopathies, which include also. Ohtahara syndrome os, also known as early infantile epileptic encephalopathy eiee is a progressive epileptic encephalopathy. Pdf metabolic causes of epileptic encephalopathy semantic. Methods a patient presenting with a severe combination of dyskinesia and neonatal epileptic. Severe cognitive, behavioural and neurological deficits. It is defined as a condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function, but this definition may be ambiguous. Ohtahara syndrome, west syndrome, early myoclonic epileptic encephalopathy, migrating partial epilepsy of infancy, and dravet.
The term epileptic encephalopathy describes a heterogeneous group of epilepsy syndromes associated with severe cognitive and behavioral disturbances. Diagnosis and management of epileptic encephalopathies in. Dec 31, 2019 the authors noted that stxbp1 should furthermore be classified as a complex neurodevelopmental disorder vs primary epileptic encephalopathy due to the high incidence of intellectual disability associated with stxbp1 with little correspondence to age of seizure onset or severity. Most patients have severe epilepsy ranging from neonatal onset developmental epileptic encephalopathy to infantile developmental epileptic encephalopathy. Autism spectrum disorder and epileptic encephalopathy. Jan 30, 2020 most patients have severe epilepsy ranging from neonatal onset developmental epileptic encephalopathy to infantile developmental epileptic encephalopathy 27 patients, 90%, of which 16 53% had. Our genetic and functional evidence demonstrate that kcnb1 mutation can result in early onset epileptic encephalopathy. Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. This expands the locus heterogeneity associated with epileptic encephalopathies. Earlyonset epileptic encephalopathies are characterized by severe seizures often infantile spasms, very frequent interictal epileptiform activity on a disorganized eeg background, developmental regression or retardation, and onset before 1 year of age. Severe neonatal epilepsy with suppressionburst pattern early epileptic encephalopathy.
Although certain syndromes are often referred to as epileptic encephalopathies, the encephalopathic effects of seizures and epilepsy may potentially occur in association with any form of epilepsy berg et al. Pediatric neurology unit, metabolicneurogenetic clinic, wolfson medical center, holon, israel objectives. Scn8arelated epilepsy with encephalopathy genetics home. P e a r l d e pa r t me nt of neu ro l og y, c hi l dre n s nati on al med i ca l ce nt e r, 1 1 1 mic. Aug 14, 2017 dravet syndrome is known to be associated with scn1a haploinsufficiency. Researchers from the university of antwerp, belgium, and numerous international collaborators report a comprehensive overview of the phenotypic and genetic spectrum of syntaxinbinding protein 1 stxbp1 encephalopathy. Although mutations in more than 50 different genes are known to cause.
The followup cohorts included 95 additional individuals 41 male and 54 female with feversensitive epileptic encephalopathy referred for early genetic testing of dravet syndrome and 62 individuals with refractory epileptic encephalopathy and seizure onset within the first 4 years of life selected from the dutch cohort. Early infantile epileptic encephalopathy11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities ogiwara et al. Epileptic encephalopathy dulac 2001 epilepsia wiley. We analyzed the genotypephenotype relationships in these and 70 previously. Genetic testing for epileptic encephalopathy blueprint. For a general phenotypic description and a discussion of genetic heterogeneity of eiee, see eiee1. We more or less assume that we understand the phenotypes associated with pathogenic variants in scn1a. Epileptic encephalopathy with continuous spikeandwave during sleep is a syndrome characterized by continuous spikeandwave during sleep, seizures and progressive decline in cognitive, behavioral and psychiatric functioning. Epileptic encephalopathies including severe epilepsy.
He was found to have frequent erratic myoclonus and myoclonic seizures. Treatment of epileptic encephalopathies springerlink. Epileptic encephalopathies are motormental retardations or cognitive disorders secondary to epileptic seizures or epileptiform activities. Sep 28, 2010 earlyonset epileptic encephalopathies are characterized by severe seizures often infantile spasms, very frequent interictal epileptiform activity on a disorganized eeg background, developmental regression or retardation, and onset before 1 year of age. The preceding neurodevelopment is normal in 50% children. Aug, 2018 early infantile epileptic encephalopathy eiee is a devastating epilepsy syndrome with onset in the first months of life. Several syndromes have been described based on their electroclinical features age. Kcnq2 encephalopathy nord national organization for. Pathogenic variants in epileptic encephalopathy are clustered in hot spots known to be critical for channel activity. Although currently described as a concept that may occur in any of the epilepsies, children with the severe early onset epilepsies are thought to.
These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in. Early infantile epileptic encephalopathy genetic and rare. Stxbp1related developmental and epileptic encephalopathy. In the classification of the international league against epilepsy eight agerelated epileptic encephalopathy syndromes are recognized. In another group of 239 patients with early infantile epileptic encephalopathy eiee, 12 patients 5% harbored mutations in the kcnq2 gene. For variants causing kcnq2 channel loss of function, ezo appeared well tolerated and potentially beneficial against refractory seizures when started early. The syndrome is outwardly characterized by tonic spasms and partial seizures within the first few months of life, and receives its more elaborate name from the pattern of burst activity on an electroencephalogram eeg. Epileptic encephalopathies refer to a group of disorders in which the unremitting epileptic activity contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone, and these can worsen over time leading to progressive cerebral dysfunction. The term epileptic encephalopathy refers to the condition where epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control.
Epileptic encephalopathy can complicate many different epileptic conditions. We retrospectively studied 23 patients with kcnq2 encephalopathy, including 11 treated with ezogabine ezo. Encephalopaties due to brain damage, medications, or systemic diseases are generally not in the scope of this definition, but they may rarely accompany the condition. Multiform,intractable and often aggressive seizures. Define epileptic encephalopathy, early infantile, type 3. As many as 60 70% can expect to eventually become seizure free either through medication or spontaneous remission. The presence of a recurrent missense variant suggests that perhaps this severe epileptic encephalopathy may be associated with a different disease mechanism, perhaps gainoffunction, as in scn2a and scn8arelated. Table 1 lists the epileptic encephalopathy syndromes. Epileptic encephalopathies are severe brain disorders of early age that manifest with.
They typically present at an early age and manifest with eeg paroxysmal activity that is often aggressive, seizures that are commonly multiform and intractable, cognitive, behavioural and neurological deficits that may be relentless and sometimes early death. Epileptic encephalopathy was selected as the topic for the 15th neurobiology of disease in children ndc conference, which was held in washington, dc, on october 78, 2015. Early infantile epileptic encephalopathy, early infantile. Early infantile epileptic encephalopathy eiee is a neurological disorder characterized by seizures.
Epileptic encephalopathy syndromes in infancy intechopen. Otahara syndrome is considered an epileptic encephalopathy because this abnormal brain activity is thought to contribute to the cognitive and behavioral impairments associated with the disorder. Most children will go on to develop additional seizure types such as infantile spasms or lennoxgastaut syndrome as they grow older. The seizures in scn8arelated epilepsy with encephalopathy include involuntary muscle contractions. Epileptic encephalopathies are characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. Scn8a mutations have recently been associated with epilepsy and neurodevelopmental disorders. Epileptic syndromes in infancy, childhood and adolescence 2d edition. Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired socialcommunication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder asd. Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. Baram and shlomo shinnar prepared an outstanding agenda that included individual presentations, questionandanswer sessions, and a future directions panel discussion with. Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone.
As this concept evolves, other syndromes may be included. Nov 14, 2017 the term epileptic encephalopathy describes a heterogeneous group of epilepsy syndromes associated with severe cognitive and behavioral disturbances. To characterize the epileptic encephalopathy in patients with iqsec2 mutations. The ilae defined an epileptic encephalopathy as a condition in which the epileptiform eeg abnormalities themselves are believed to contribute to a progressive disturbance in cerebral function. A 5dayold boy born full term without complications who presented with hypotonia, apnea, irritability, and jitteriness. Severe brain disorders in which the epileptic electrical discharges may contribute to progressive psychomotor dysfunction.
Kcnq2 variants cause neonatalonset epileptic encephalopathy of widely varying severity. With the advent of nextgeneration sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates. Metabolic causes of epileptic encephalopathy j o ey u e z h o uy ua n dp h i l l i pl. Seizures are the presenting symptom in 80% children and neuropsychological deterioration in the. Childhood epileptic encephalopathy with continuous spikeandwave during sleep csws, including landaukleffner syndrome lks the ilae task force report in 2001 engel, 2001 classified landaukleffner syndrome lks and epileptic encephalopathy with continuous spikeandwave during sleep csws under the heading of epileptic encephalopathies. A distinctive generalized developmental and epileptic encephalopathy, vlaskamp et al. These disorders vary in their age of onset, developmental outcome, etiologies, neuropsychological deficits, electroencephalographic eeg patterns, seizure types, and prognosis, but all may have. Ohtahara syndrome, west syndrome, early myoclonic epileptic encephalopathy, migrating partial epilepsy of infancy, and dravet syndrome are. Kcnq2 encephalopathy nord national organization for rare.
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