Sep 18, 2017 scn8a mutations have recently been associated with epilepsy and neurodevelopmental disorders. The signs and symptoms of this condition typically begin in infancy. With the advent of nextgeneration sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates. Early infantile epileptic encephalopathy genetic and rare. Dec 20, 2019 epileptic encephalopathy, early infantile, epileptic encephalopathy, early infantile, 5. Multiform,intractable and often aggressive seizures. Epileptic encephalopathy with continuous spikeandwave during sleep. The main feature of neonatal epileptic encephalopathy nee is the onset within hours of birth of a severe seizure disorder that does not respond to anticonvulsant drugs and can be fatal. Investigation of seizures in infants epilepsy society. Scn8arelated epilepsy with encephalopathy is a condition characterized by recurrent seizures epilepsy, abnormal brain function encephalopathy, and intellectual disability.
Surgical treatment of an early infantile epileptic encephalopathy with suppressionburst associated and focal cortical dysplasia. Focal abnormalities of the white matter generally area of low perfusion are appreciated through magnetic resonance. Ohtahara syndrome also known as early infantile epileptic encephalopathy this is a rare epilepsy syndrome usually presenting in the first few days or weeks of life, but sometimes as late as three months of age. This chronic encephalopathy may be reversed with suppression of the discharges. Early severe neonatal and infantile epileptic encephalopathies. In many affected individuals, seizures stop in early childhood. Cad mutations and uridineresponsive epileptic encephalopathy. This study aimed to broaden the phenotypicspectrum of disease related with scn8a mutations.
The term benign is replaced by the terms selflimited and. In the classification of the international league against epilepsy eight agerelated epileptic encephalopathy syndromes are recognized. Early infantile epileptic encephalopathy eiee is a neurological disorder characterized by seizures. Most children will go on to develop additional seizure types such as infantile spasms or lennoxgastaut syndrome as they grow older. A longer polyalanine expansion mutation in the arx gene causes early infantile epileptic encephalopathy with suppressionburst pattern ohtahara syndrome. Impaired m current in kcnq2 epileptic encephalopathy. Rugtveit described infantile spasms in 2 brothers who, like 5 others, had nonspecific xlinked mental retardation. Therapeutic approach to epileptic encephalopathies wiley online. Epileptic encephalopathy in children possibly related to. In the case of the revised classification, a first proposal. Herein, we define the phenotypic spectrum of scn2a encephalopathy. The preceding neurodevelopment is normal in 50% children. To move a condition from its genetic definition to a comprehensive syndrome description is an important step forward, and vlaskamp et al.
This expands the locus heterogeneity associated with epileptic encephalopathies. Nevertheless, failure of treatment to improve either seizures or encephalopathy is commonplace, as epileptic encephalopathies are highly resistant to treatment. Early recognition of the clinical signs can improve treatment outcome, as well as reduce the incidence of risk factors. To identify the pathogenic gene of a chinese family, in which six members suffered from epilepsy, wholeexome sequencing was performed. Review article diagnosis and management of epileptic. These syndromes include early myoclonic encephalopathy and ohtahara syndrome in the neonatal. We observed a clear loss of function for all mutations. Stxbp1 encephalopathy with epilepsy is a condition characterized by recurrent seizures epilepsy, abnormal brain function encephalopathy, and intellectual disability. Neonatal epileptic encephalopathy caused by mutations in the. Aug 14, 2017 dravet syndrome is known to be associated with scn1a haploinsufficiency. Severe cognitive, behavioural and neurological deficits. Epileptic encephalopathy panel billing updates effective010119. Hepatic encephalopathy he is a neurologic syndrome resulting from the synergistic action of multiple pathologic factors, which are discussed in a companion article.
Patients with eme and ohtahara syndrome typically undergo exhaustive evaluation. 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 encephalopathy syndromes in infancy intechopen. 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. Early infantile epileptic encephalopathy acquired or congenital abnormal cortical development. The appropriate billonly code, as shown below, is assigned by genetics staff. 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. A 5dayold boy born full term without complications who presented with hypotonia, apnea, irritability, and jitteriness. 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. We describe the epileptic phenotype and neurocognitive. In the classification of the international league against epilepsy eight agerelated epileptic encephalopathy syndromes are. Current understanding and neurobiology of epileptic.
The onset of this epileptic encephalopathy is between 2 months and 12 years of age with a peak at 47 years of age. Kcnq2 encephalopathy nord national organization for rare. The chronic cognitive deficits are an adult form of epileptic encephalopathy. Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. We sequenced the exomes of 264probands,andtheirparents,andconfirmed329denovomutations. These syndromes include early myoclonic encephalopathy and ohtahara syndrome in the neonatal period, west. While many of these disorders are caused by neuronal channelopathies, the role of synaptic and related neuronal proteins are increasingly being described. There are two well described epileptic encephalopathies in this age group. A significant proportion of cases have a genetic origin, and the most frequently mutated gene is kcnq2, encoding kv7. Systemic lupus erythematosus sle and epilepsy have been variably associated 1020%, and epilepsy has also been associated with the presence of antiphospholipid antibodies apl,, anticardiolipin antibodies, antinuclear antibodies.
Severe neonatal epilepsy with suppressionburst pattern early epileptic encephalopathy. Note childhood epilepsy with centrotemporal spikes, atypical childhood epilepsy with centrotemporal spikes, epileptic encephalopathy with continuous spikeandwave during sleep and landau kleffner syndrome are syndromes that have in common certain eeg features, with variable severity of focal seizures and neurocognitive impairment. Further patients and studies are needed to improve our understanding of the phenotypic spectrum and elucidate the effects of the variants on protein function. 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. The report of the international league against epilepsy ilae task force on classification and terminology includes 8 syndromes under epileptic.
Some forms of earlyonset epileptic encephalopathy eoee have been associated with variants in scn2a, which encodes the brain voltagegated sodium channel nav1. Epileptic syndromes in infancy, childhood and adolescence 2d edition. The signs and symptoms of this condition typically begin in infancy but can first appear later in childhood or early adulthood. 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. Can sodium valproate improve learning in children with epileptiform bursts but without clinical seizures.
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. Early onset epileptic encephalopathy with suppression. What is early infantile epileptic encephalopathy eiee. Epileptic encephalopathies including severe epilepsy. Growing evidence demonstrates that pathogenic genetic variants are a common risk factor for ee, including variants in the. Several associations between epilepsy and immunological diseases have been described table 1, table 2. Some patients with nee have shown biochemical changes in the cerebrospinal fluid csf and urine that indicate reduced activity of aromatic l amino acid. Early infantile epileptic encephalopathy with suppressionburst ohtahara syndrome early infantile epileptic encephalopathy, or ohtahara syndrome, is a severe neurologic condition first described in 1976 9. In addition, target nextgeneration sequencing ngs was performed on 178.
Autism spectrum disorder and epileptic encephalopathy. Early myoclonic epileptic encephalopathy possibly due to metabolic disorders. Strikingly, 5 of 7 mutations exhibited a drastic dominant. Their data supported a multifactorial model involving polygenic determination of susceptibility and requiring additional environmental factors such as anoxia, birth trauma, or immunization. Nevertheless, failure of treatment to improve either seizures or encephalopathy is commonplace, as epileptic encephalopathies are highly resistant to treatment 3. Early epileptic encephalopathy with suppressionbursts and. In the classification of the international league against epilepsy eight age related epileptic encephalopathy syndromes are recognized. Ohtahara syndrome os, also known as early infantile epileptic encephalopathy eiee is a progressive epileptic encephalopathy. Early infantile epileptic encephalopathies is group of disorders comprises ohtahara syndrome or early infantile epileptic encephalopathy eiee, early. Treatment of epileptic encephalopathies springerlink. Nov 14, 2017 the term epileptic encephalopathy describes a heterogeneous group of epilepsy syndromes associated with severe cognitive and behavioral disturbances. The definition of epilepsy requires the occurrence of at least one epileptic seizure. The gabra1 r214c variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wildtype wt.
Pdf epileptic encephalopathies represent a group of devastating epileptic. Dec 31, 2012 epileptic encephalopathy can complicate many different epileptic conditions. May 12, 2020 epileptic encephalopathy, early infantile, 9. Early infantile epileptic encephalopathy 25 genetic and. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition. Chronic epileptic encephalopathy in adult patients with.
Epilepsy of infancy with migrating focal seizures migrating partial seizures in infancy10,11 although this would appear to be a rare syndrome it is probably underrecognised, like most new epilepsy syndromes. It is defined as a condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in. New terminology is introduced such as developmental and epileptic encephalopathy. This group of disorders comprises ohtahara syndrome or early infantile epileptic encephalopathy eiee, early myoclonic encephalopathy eme, and malignant. Cdkl5 mutations as a cause of severe epilepsy in infancy. Early infantile epileptic encephalopathy genetic and. Epileptic syndromes in infancy, childhood and adolescence, 5th, bureau m, genton p, dravet c eds, libbey eurotex, 2012. Seizures are the presenting symptom in 80% children and neuropsychological deterioration in the. Prasad please note, due to essential maintenance online purchasing will be unavailable between 08. Infants have primarily tonic seizures which cause stiffening of muscles of the body. The identification and treatment of additional cad patients over a longer period is necessary to fully define the phenotypic spectrum and to corroborate the beneficial. He was found to have frequent erratic myoclonus and myoclonic seizures. Screening of followup cohorts comprising 157 cases in total identified 4. It has an early onset and symptoms generally occur before the.
Scn8arelated epilepsy with encephalopathy genetics home. Pathophysiology of and therapeutic options for a gabra1. Our genetic and functional evidence demonstrate that kcnb1 mutation can result in early onset epileptic encephalopathy. Attention is drawn to some reflex epileptic traits. Early infantile epileptic encephalopathy eiee, also called ohtahara syndrome, is a rare disorder characterized by infantile spasms.
Hcn1 gainoffunction mutations a new cause of epileptic. The inclusion of 57 patients in a multicenter study provided an excellent, detailed delineation of the seizure syndrome. Probatory uridine administration might be considered in severely affected patients with anisopoikilocytosis and epileptic encephalopathy prior to a confirmed genetic diagnosis. Click on the link to view a sample search on this topic. Twelve patients with an scn2a epileptic encephalopathy underwent electroclinical phenotyping. Several syndromes have been described based on their. 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.
Epileptic encephalopathy ee is a severe neurological condition in which a patients epileptic activity results in additional cognitive or behavioral impairments beyond those expected from the underlying etiology alone. Epileptic encephalopathies are severe forms of infantileonset epilepsy often complicated by severe neurodevelopmental impairments. Genetic testing of epileptic encephalopathies of infancy. It may be years before maximal improvement in cognition occurs. These spikewave discharges may be associated with chronic cognitive deficits. The role of genetic testing lemke, syrbe 3 this document was downloaded for personal use only.
Epileptic encephalopathy in infants and children ncbi. Epileptic encephalopathies are severe brain disorders of early age that manifest with. Later in 2010, researchers defined epileptic encephalopathy as a condition where the epileptic activity itself may contribute to severe cognitive and behavioral. The main goal of treatment is to stop the peculiar course of epilepsy, operating on three parameters. 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. A diagnostic scheme for people with epileptic seizures and with epilepsy proposed by ilae commission 2001 engel, jr.
Sporadic infantile epileptic encephalopathy caused by. An approach volume 40 issue 1 suvasini sharma, asuri n. The seizures in scn8arelated epilepsy with encephalopathy include involuntary muscle contractions that. Pdf epileptic encephalopathies in infants and children.
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. Severe brain disorders in which the epileptic electrical discharges may contribute to progressive psychomotor dysfunction. Diagnosis and management of epileptic encephalopathies in. Since 2003, we have performed molecular analyses in a large series of patients with ds, 27% of whom were negative for mutations or rearrangements in scn1a. It is a rare entity, with a relative prevalence to west syndrome estimated at 140 or less 9. These disorders vary in their age of onset, developmental outcome, etiologies, neuropsychological deficits, electroencephalographic eeg patterns, seizure types, and prognosis, but all may have. The distinctions between the tw and the epileptic discharge include more acute narrowangled, briefer, and frontopolar emphasis for generalized spike waves. Oct 26, 2016 early infantile epileptic encephalopathy eiee is a neurological disorder characterized by seizures. Pubmed is a searchable database of medical literature and lists journal articles that discuss early infantile epileptic encephalopathy 25. Highlights adults with generalized epilepsy may have frequent bilateral spikewave discharges.