Patient Description We describe a patient with EIEE13 (de novo heterozygous pathogenic mutation in SCN8A - p.Ile240Val (ATT>GTT)) who presented prenatally with maternally reported intermittent, rhythmic movements that, when observed on ultrasound, were [jhu.pure.elsevier.com]

The general purpose of the present study was to analyze specific kinds of data from a large series of epileptic patients to focus the significance of the findings, particularly in relation to previously published results. [books.google.it]

Dravet syndrome (DS) is a variant of epileptic encephalopathy that presents in infancy with gradually varying seizure types. [neurologyindia.com]

Part of patients with SCN8A mutations presented only mental retardation without epilepsy [ 11 ]. [bmcmedgenet.biomedcentral.com]

Diagnosis [ edit ] The diagnosis is based on the clinical presentation and on typical electroencephalographic patterns. [19] Treatment [ edit ] Treatment outlook is poor. [en.wikipedia.org]

• Epilepsy

  Background SCN8A mutations are rare and cause a phenotypically heterogeneous early onset epilepsy known as early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558). [jhu.pure.elsevier.com]

  The other one affected member presented with refractory epilepsy and developmental regression. She died from sudden unexpected death in epilepsy (SUDEP) at 17-year-old. [bmcmedgenet.biomedcentral.com]

  CHRNA2 ADNFLE, focal epilepsy 20301348 CHRNA4 ADNFLE, focal epilepsy 20301348 CHRNA7 15q13.3 recurrent microdeletion syndrome, risk factor for idiopathic generalized epilepsy and neurodevelopmental disorders 21290787,20502679 CHRNB2 ADNFLE, focal epilepsy [tests.labmed.washington.edu]

  With increasing genetic studies in common epilepsies, the middle ground between the extremes of mild familial epilepsies and severe epilepsy encephalopathies will be increasingly explored. [karger.com]

  With more than 80 chapters, Pellock’s Pediatric Epilepsy now contains a full discussion of the spectrum of epilepsy disorders, not just seizures. [books.google.com]

• Developmental Delay

  West syndrome or Infantile spasms (IS) is the most common type of EE and is characterized by a triad of symptoms: spasms, hypsarrhythmia, and developmental delay/regression. [centogene.com]

  All reported individuals with this condition, including the present case manifest global developmental delay, seizures, progressive postnatal microcephaly, hypotonia, thin corpus callosum, cerebral atrophy, delayed myelination and white matter changes [readbyqxmd.com]

  Patients with EIEE2 have a specific phenotype of early onset seizures, developmental delay and morphologic abnormalities of the hands, limbs and face. EIEE2 is an X-linked disorder. [molgen.ua.ac.be]

  Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015 Nov;138(Pt 11):3238-50. doi: 10.1093/brain/awv263. Epub 2015 Sep 17. [rarediseases.org]

  Most parents would rather suffer anything themselves than watch their child go through something like epilepsy with a developmental delay. [verywell.com]

• Pneumonia

  Death is often due to pneumonia or other complications of a complex disability. Etiology EIEE may be the result of different etiologies. Many cases have been associated with structural brain abnormalities. [orpha.net]

• Encephalopathy

  SCN8A Epileptic Encephalopathy: Detection of Fetal Seizures Guides Multidisciplinary Approach to Diagnosis and Treatment. [jhu.pure.elsevier.com]

  […] infantile epileptic encephalopathy type 25 (SLC13A5) TEST DETAILS Cost of Early infantile epileptic encephalopathy type 25 (SLC13A5) Test in India [dnalabsindia.com]

  […] epileptic encephalopathy 2 XLD 18 DNM1 602377 early infantile epileptic encephalopathy, 31 AD 7 DOCK7 615730 early infantile epileptic encephalopathy 23 AR 3 EEF1A2 602959 mental retardation- 38; early infantile epileptic encephalopathy type 33 AD 3 [centogene.com]

  GABRB3 Epileptic encephalopathy 23934111,26645412 GABRG2 Epileptic encephalopathy, Dravet-like 11326275 GNAO1 Epileptic encephalopathy 23993195 GRIN1 Early infantile epileptic encephalopathy 25864721,26933583 GRIN2A Epilepsy aphasia syndromes 23933818,23933819,23933820 [tests.labmed.washington.edu]

  Electroclinical features of epileptic encephalopathy caused by SCN8A mutation. [ncbi.nlm.nih.gov]

• Ataxia

  Registry Alternating Hemiplegia Of Childhood 2 AHC2 614820 Genetic Test Registry Angelman Syndrome Angelman Syndrome Chromosome Region, Included Happy Puppet Syndrome AS ANCR 105830 Genetic Test Registry Cognitive Impairment With Or Without Cerebellar Ataxia [ukgtn.nhs.uk]

  Early infantile epileptic encephalopathy, ferro-cerebro-cutaneous syndrome 26993267,24259288,24706016 PLCB1 Epilepsy with migrating focal seizures in infancy (EMFSI); epileptic encephalopathy; AR inheritance, deletions reported 22690784,26818157 PNKP Ataxia [tests.labmed.washington.edu]

  […] apraxia; MCSZ – Microcephaly seizures and developmental delay; GEFSP – Generalized epilepsy with febrile seizures plus; CIAT – Cognitive impairment with or without cerebellar ataxia; SFN - Small fiber neuropathy; CIP – Congenital insensitivity to pain [centogene.com]

  EIEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy. [uniprot.org]

  Página 110 - Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. ‎ [books.google.es]

• Neonatal Seizures

  Abstract Neonatal seizures are a common problem encountered or suspected by those caring for neonates. The estimated incidence of newborns affected is between 0.1% to 0.5%. [neoreviews.aappublications.org]

  Punctate white matter lesions in full-term infants with neonatal seizures associated with SLC13A5 mutations. Eur J Paediatr Neurol. 2017 Mar;21(2):396-403. doi: 10.1016/j.ejpn.2016.11.002. Epub 2016 Nov 19. PubMed PMID: 27913086. [rarediseases.org]

  Initially described as the gene for Benign Familial Neonatal Seizures, dominant negative de novo mutations in this gene are also found in epileptic encephalopathies with neonatal onset. EIEE8 – ARHGEF9. [euroepinomics.wordpress.com]

  KCNQ2 Encephalopathy (KCNQ2E) Synonyms • KCNQ2-Related Neonatal Epileptic Encephalopathy • Early infantile epileptic encephalopathy 7 (EIEE7) Related Disorders • Benign Familial Neonatal Convulsions/Seizures (BFNC/S) General Discussion KCNQ2 typically [kcnq2cure.org]

  […] familial hemiplegic migraine-3 AD 131 SCN2A 182390 benign familial neonatal-infantile seizures type 3; early infantile epileptic encephalopathy 11 AD 60 SCN8A 600702 Cognitive impairment with or without cerebellar ataxia; early infantile epileptic encephalopathy [centogene.com]

• Focal Seizure

  Normal Normal – Untreated, seizures resolved III-4 F 6y, 9 mo 6 m Focal seizure Normal Normal Normal (6 m) Seizures free from 1-year-old with VPA III-5 F 2 y, 9 mo 6 m Focal seizure Normal Normal – No seizures after 1 years old with VPA In addition, [bmcmedgenet.biomedcentral.com]

  […] spasms, and absence and focal seizures). [ncbi.nlm.nih.gov]

  epileptic encephalopathy 9425895,20437616 KCNQ3 Benign familial infantile seizures 9425900 KCNT1 Epilepsy with migrating focal seizures in infancy (EMFSI), epileptic encephalopathy, autosomal dominant nocturnal frontal lobe epilepsy 23086396,23086397,26122718,26140313 [tests.labmed.washington.edu]

  In addition, epilepsy-related surgery may be helpful in children with localized/focal seizures. [centogene.com]

  About 1 out of 3 infants with OS may develop other seizure types, such as partial or focal seizures (start in one area of the brain), atonic, myoclonic or generalized tonic clonic seizures. Infants with OS may also develop infantile spasms. [epilepsy.com]

• Generalized Seizure

  […] presenting as tonic seizures (a generalized seizure involving a sudden stiffening of the limbs). [4] Other seizure types that may occur include partial seizures, clusters of infantile spasms, and, rarely, myoclonic seizures. [en.wikipedia.org]

  The first seizure is often triggered by a fever. As time passes, the child has many types of seizures, including general seizures, partial seizures, and myoclonic jerks. The initial EEG is normal but slows over time. [verywell.com]

  Epilepsy onset was at 5 months old, with focal seizures followed by secondary generalization. [bmcmedgenet.biomedcentral.com]

  Initial symptoms include poor suck reflex and general floppiness, followed by epileptic seizures. [intechopen.com]

The diagnostic workup of EIEEs remains challenging because of frequent difficulties in defining etiologies. [dnatesting.uchicago.edu]

We identified 26 patients with Infantile Epileptic Encephalopathy (IEE) of unknown etiology despite extensive workup and without any specific epilepsy syndromic phenotypes. [journals.plos.org]

Diagnostic workup In early myoclonic encephalopathy, EEG is characterized by a "burst-suppression" pattern with bursts of spikes, sharp waves, and slow waves, which are irregularly intermingled and separated by periods of electrical silence. [intechopen.com]

• Spike-and-Slow-Waves

  […] paroxysms of polyspikes or spikes-slow waves.  Ictal EEG  Varies according to seizure type. 16. [slideshare.net]

  EEG at age of 8 months showed sharp and spike waves in the right frontal during sleeping period, and 3–4 Hz slow-wave complexes in the occipital region during awake period. Seizures attacked 1–2 times per day. [bmcmedgenet.biomedcentral.com]

• Multifocal Spikes

  Diagnosis Hypsarrhythmia, the typical interictal EEG finding, consists of a disorganized pattern with asynchronous, very high amplitude slowing and frequent multifocal spike and sharp wave discharges. [intechopen.com]

• 3-4 Hz Spikes

  Childhood absence epilepsy with tonicclonic seizures and electroencephalogram 3-4-Hz spike and multispikeslow wave complexes: linkage to chromosome 8q24. Am J Hum Genet. ‎ [books.google.es]

SCN8A Epileptic Encephalopathy: Detection of Fetal Seizures Guides Multidisciplinary Approach to Diagnosis and Treatment. [jhu.pure.elsevier.com]

Risk and treatment management includes, but is not limited to [6] : For ALDH7A1 related pyridoxine-dependent epilepsy and PNPO related pyridoxamine 5′-phosphate oxidase deficiency: Treatment Pyridoxine should be used For KCNQ2 related early infantile [swisscheckup.com]

Brand-new chapters in the drug and diet section cover perampanel, ezogabine, and lacosamide, while the existing chapters on major medical treatments have been comprehensively updated to reflect the latest trials and studies. [books.google.com]

This article reviews the various seizure types, etiologies, diagnostic modalities, and treatment options for neonates with seizures and seizure-like episodes. [neoreviews.aappublications.org]

Prognosis Children have a poor prognosis, experiencing developmental regression, and eventual severe mental retardation. [intechopen.com]

Prognosis Prognosis is poor with death usually occurring in infancy (50% before age of 2). Survivors have severe psychomotor impairments with continuing seizures. The documents contained in this web site are presented for information purposes only. [orpha.net]

Prognosis The prognosis is related to the underlying disorder. The severity of developmental impairment varies with the type of epilepsy. Early infantile epileptic encephalopathy (Ohtahara syndrome) The prognosis is very poor. [emedicine.medscape.com]

 Poor prognosis with occ. early death. 3.  Neonates.  Early myoclonic encephalopathy.  Ohtahara syndrome.  Infancy.  West syndrome.  Dravet syndrome.  Childhood.  Myoclonic astatic epilepsy.  Epileptic encephalopathy with CSWS including Landau [slideshare.net]

There are many manifestations of epilepsy and, therefore, a diversity of factors in underlying pathology, responses to treatment and prognosis. [books.google.com]

Etiology No clear etiology is found in approximately 40% of cases ( Hrachovy, 2008 & Vigevano, 1992). [intechopen.com]

Etiology EIEE may be the result of different etiologies. Many cases have been associated with structural brain abnormalities. [orpha.net]

The developmental prognosis partially depends on the etiology. When classified by etiology, normal development was described in 51% of cryptogenic cases versus only 6% of symptomatic cases. [emedicine.medscape.com]

This article reviews the various seizure types, etiologies, diagnostic modalities, and treatment options for neonates with seizures and seizure-like episodes. [neoreviews.aappublications.org]

The diagnostic workup of EIEEs remains challenging because of frequent difficulties in defining etiologies. [dnatesting.uchicago.edu]

Particular updates include full coverage of new developments in epidemiology, genetics, classification, imaging, drug therapy and other treatments. [books.google.com]

Página 67 - Socioeconomic characteristics of childhood seizure disorders in the New Haven area: an epidemiologic study ‎ Página 67 - Epilepsy after penetrating head injury. I. Clinical correlates: a report of the Vietnam Head Injury Study. [books.google.es]

Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch. Dis. Child. 1999; 81(5):431-3. PMID: 10519720 Trevathan, E, et al. The descriptive epidemiology of infantile spasms among Atlanta children. [invitae.com]

Relevant External Links for SLC13A5 Genetic Association Database (GAD) SLC13A5 Human Genome Epidemiology (HuGE) Navigator SLC13A5 Atlas of Genetics and Cytogenetics in Oncology and Haematology: SLC13A5 No data available for Genatlas for SLC13A5 Gene Human [genecards.org]

Pathophysiology The underlying mechanisms of these disorders are still poorly understood. [intechopen.com]

While these gene discoveries initially had no direct link to the more severe epileptic encephalopathies, they laid the general pathophysiological concept, such as the channelopathy concept of the human epilepsies [Steinlein, 2004], which eventually provided [karger.com]

Pathophysiology The epileptic encephalopathies are a group of age-specific epilepsy syndromes of diverse etiologies that share the potential for causing significant cognitive impairment. [emedicine.medscape.com]

Polysomnographical assessment of the pathophysiology of West syndrome. Brain Dev. 2001;23(7):523-7.Hayashi M. Neuropathology of the limbic system and brainstem in West syndrome. [malattierare.regione.veneto.it]

Because several causes of seizures in newborns require rapid recognition and treatment to prevent further injury, early recognition is important. Seizures in newborns frequently have more subtle clinical manifestations than in older children. [neoreviews.aappublications.org]

However, the high cost of the genetic analysis has prevented the parents from going ahead with the test. At present, the child is on a regular follow-up. He has recently been started on ketogenic diet. [neurologyindia.com]

Clinical Actionability Tools Clinical Actionability tools support the curation process is to identify those human genes that, when significantly altered, confer a high risk of serious disease that could be prevented or mitigated if the risk were known [clinicalgenome.org]

Prevention No information is available. Genetic counseling might be helpful. 6.6. [intechopen.com]

Clinico-electrical evolution in pre-hypsarrhythmic stage: towards prediction and prevention of West syndrome. Brain Dev. 2001;23(7):482-7.Ohtsuka Y, Kobayashi K, Ogino T, Oka E. Spasms in clusters in epilepsies other than typical West syndrome. [malattierare.regione.veneto.it]