Journal of Pediatric Epilepsy - Volume 1, issue 3

Authors: Porter, Brenda E.

Article Type: Other

DOI: 10.3233/PEP-2012-022

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 133-133, 2012

Authors: Sheidley, Beth Rosen | Poduri, Annapurna

Article Type: Review Article

Abstract: In the last decade, major advances have been made in our understanding of the genetic basis of epilepsy. Genetic testing for over two dozen epilepsy-related genes is now clinically available, and healthcare providers who manage patients with epilepsy are faced with incorporating genetic information into their assessment and treatment plans. Although the clinical applications of genetic test results in the setting of epilepsy may be somewhat limited, an argument for the utility of testing can be made based upon the potential impact on treatment options, the ability to provide prognostic information, and the psychological, medical, and reproductive implications for patients …and their family members. Clinicians who incorporate genetic testing into their evaluation of patients with epilepsy must be knowledgeable about epilepsy phenotypes and epilepsy genes, have expertise in eliciting a genetic family history that encompasses not only epilepsy but a broader range of relevant medical conditions, and possess a thorough understanding of genetic testing methods and outcomes. Given the complexity of genetic test results, it is crucial that informed consent to discuss the risks, benefits, and limitations of genetic testing take place with patients prior to testing. In addition, many patients may benefit from genetic counseling to discuss testing options or results, address family impact or reproductive issues, and obtain access to support resources. Show more

Keywords: Epilepsy, genetics, genetic counseling, epilepsy genes

DOI: 10.3233/PEP-2012-023

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 135-142, 2012

Authors: Wusthoff, Courtney J.

Article Type: Review Article

Abstract: Benign familial neonatal epilepsy (BFNE), previously benign familial neonatal seizures, is a relatively rare epilepsy syndrome arising in newborns. The genetic basis for this syndrome has recently been defined. This review uses a case to illustrate the challenges in the clinical approach to diagnosis in neonatal epilepsy, and gives the clinician a summary of the genetic basis for BFNE. Finally, an overview of counseling and clinical treatment of BFNE is discussed.

Keywords: Newborn infant, neonate, seizures, benign neonatal epilepsy, benign familial neonatal seizures, KCNQ potassium channels

DOI: 10.3233/PEP-2012-024

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 143-149, 2012

Authors: Olson, Heather E. | Poduri, Annapurna

Article Type: Review Article

Abstract: CDKL5 mutations have been recognized as a cause of early onset epileptic encephalopathy, particularly in females with atypical Rett syndrome. After presenting a case with a CDKL5 mutation, we review the literature on reported cases of CDKL5 mutations and summarize the clinical phenotype including epilepsy, electrophysiology, neuroimaging, physical examination, development, and other clinical features. The typical phenotype associated with a CDKL5 mutation is early onset epilepsy in a girl with severe developmental delay and hypotonia. Other features frequently include microcephaly, growth retardation, and Rett-like features (deceleration of head growth, hand stereotypies, autistic features, breathing dysfunction, and …sleep disturbances). Neuroimaging may be normal or show atrophy or T2 signal change in the posterior, temporal, or periventricular white matter. Epilepsy commonly includes infantile spasms and seizures with multiple distinct phases within one seizure epoch. Male cases with a similar phenotype are also described. CDKL5 gene testing should be considered in patients of both genders with unexplained early onset epilepsy, developmental delay/intellectual disability, and hypotonia with or without microcephaly, growth retardation, poor visual fixation, or Rett-like features. Making the genetic diagnosis of a CDKL5 mutation in a child with early onset epileptic encephalopathy provides a precise diagnosis that allows for counseling about prognosis and genetic counseling. Show more

Keywords: CDKL5, early onset epilepsy, epileptic encephalopathy, Rett syndrome

DOI: 10.3233/PEP-2012-025

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 151-159, 2012

Authors: Jähn, Johanna A. | Helbig, Ingo

Article Type: Review Article

Abstract: Structural genomic variations, gains or losses of chromosomal material, are increasingly recognized in human health and disease and represent a major source of interindividual genetic variation. In seizure disorders, structural genomic variations are important on at least three different scales, ranging from (1) chromosomal disorders or gross chromosomal rearrangements, (2) genomic disorders and rare microdeletions and microduplications, to (3) small deletions and duplications of known epilepsy candidate genes. While structural genomic variations in known epilepsy candidate genes such as SCN1A and chromosomal disorders are both rare, possibly pathogenic microdeletions and microduplications can be identified in up to 10% of …patients with seizure disorders. This review aims to provide an overview of the different classes of structural genomic variants pertaining to the epilepsies, guide the clinician in interpreting these variants and discuss the lessons learned from structural genomic variants for future genetic technologies. Particular reference will be paid to the phenotypes of the frequently encountered 15q13.3 and 16p13.11 microdeletions, as these variants may pose a challenge in clinical practice. Show more

Keywords: Copy number variation, epilepsy, seizure disorders, structural genomic variations, SCN1A, 15q13.3

DOI: 10.3233/PEP-2012-026

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 161-169, 2012

Authors: Paciorkowski, Alex R. | Porter, Brenda E.

Article Type: Review Article

Abstract: MEF2C haploinsuffiency syndrome is one of several recently identified conditions that have abnormalities in multiple areas of neurologic function. Infant-onset myoclonic seizures and infantile spasms are common, but later-onset forms of epilepsy have been reported as well. Most children have a hyperkinetic movement disorder consisting of frequent stereotypies that aid in clinical recognition of the syndrome. There is evidence that MEF2C is a member of several key neurodevelopmental genetic pathways, and the hope is that in the future one or more of these pathways may be amenable to pharmacologic modification with the goal of symptom improvement.

Keywords: MEF2C haploinsufficiency, infantile spasms, infant myoclonic epilepsy, hyperkinesis

DOI: DOI 10.3233/PEP-2012-027

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 171-178, 2012

Authors: Singhal, Nilika S. | Sullivan, Joseph E.

Article Type: Review Article

Abstract: Mutations in the PCDH19 gene are an important cause of early-onset epilepsy in females along the spectrum of epilepsy in females linked to mental retardation. Patients often have cognitive impairment or behavioral disorders, but the severity of epilepsy and co-morbidities are quite variable. Genetic testing for this condition is crucial in order to provide the best medical management of seizures along with appropriate genetic counseling for the families of affected individuals.

Keywords: PCDH19, epilepsy in females linked to mental retardation

DOI: 10.3233/PEP-2012-028

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 179-184, 2012

Authors: Ho, Gladys | Gold, Wendy | Williamson, Sarah L. | Christodoulou, John

Article Type: Other

DOI: 10.3233/PEP-2012-029

Citation: Journal of Pediatric Epilepsy, vol. 1, no. 3, pp. 185-186, 2012