Genetic testing in the epilepsies—developments and dilemmas

Poduri, Annapurna; Sheidley, Beth Rosen; Shostak, Sara; Ottman, Ruth

doi:10.1038/nrneurol.2014.60

Cited by 70 publications

(69 citation statements)

References 63 publications

(60 reference statements)

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“…Their approach parallels the approach undertaken now in the clinic, which is far from perfect but offers the possibility of genetic diagnosis to an increasing number of children with severe early onset epilepsy (8). Their work nicely demonstrates the value of collaborative sequencing efforts and functional validation of suspected variants.…”

Section: Hcn1 Gain-of-function Mutations -A New Cause Of Epileptic Enmentioning

confidence: 86%

HCN1 Gain-Of-Function Mutations – a New Cause of Epileptic Encephalopathy

Poduri¹

2014

Epilepsy Curr

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Section: Hcn1 Gain-of-function Mutations -A New Cause Of Epileptic Enmentioning

confidence: 86%

HCN1 Gain-Of-Function Mutations – a New Cause of Epileptic Encephalopathy

Poduri¹

2014

Epilepsy Curr

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“…Many previous studies reported that up to 50% of patients with epilepsy were treated at least intermittently with more than one AED. In these cases, identification of a specific genetic cause could have a significant personal value, even in the absence of clear clinical utility (30)(31)(32). Assortment of AED to control epileptic attack should be based on several factors, including mechanism of action, side effect profile, and AED-AED interactions (7,33).…”

Section: Discussionmentioning

confidence: 99%

Evidence-Based Pharmacotherapy of Epilepsy

2014

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Background: Due to the narrow therapeutic window of the AEDs prescription, their side effects and efficacy are the most important items that should be considered in epileptic patients. Objectives: This study aimed to investigate evidence-based pharmacotherapy in epileptic patients. Patients and Methods: Data were collected Cross-sectionally from patients (n = 24) registered at Kashani Epilepsy Ward in Isfahan. Demographic, clinical, hematology and biochemical data were recorded in d-base and analyzed using SPSS application for windows. Results: The frequency of polypharmacy was 79% in which 50% of epileptic patients received 3 to 4 AEDs. The onset of seizure was under 16 years old in 70% of patients. Fourteen varieties of AEDs were used, among them valproic acid (Depakote) was the most administered drugs. Prescriptions of two patients consisted of 4 and 6 AEDs: patient with code No. 575 (carbamazepine, topiramate, clobasam, lamotrigine) and another one with code No. 587 (oxcarbamazepine, phenytoin, gabapentin, valproic acid, clonazepam, lamotrigine). Red blood cell counts, hemoglobin and hematocrit in patients under more than one drug treatment were significantly lower than patients with AED monotherapy. Conclusions: AEDs are well-recognized to control seizure attacks. In clinical practice, the older generation of AEDs such as carbamazepine (CBZ), valporic acid (VPA), phenytoin (PHT), topiramate (TOP) and lamotrigine (LAMO) might need monitoring serum levels. Nonrational polypharmacy in terms of simultaneous using of both AEDs inducer and inhibitor could cause sedation, dizziness, and cognitive adverse effects. Further studies are needed to confirm these associations. Finally, to avoid polypharmacy that could arise side effects, a sufficient intervention for each AED to decide on its continuation, interruption or the number of drugs should be attempted. Combinations based on CBZ + VP, VP + TOP, CBZ + TOP, VP + LAMO, and TOP + LAMO could cause pharmacokinetic interactions.

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“…Not unlike other genetically determined disorders, the value of genetic testing depends on the following four factors: analytic validity, clinical validity, clinical utility, and personal utility [29].…”

Section: Circumstances Of Genetic Testingmentioning

confidence: 99%

The Genetics of the Epilepsies

Achkar

Olson

Poduri

et al. 2015

Curr Neurol Neurosci Rep

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While genetic causes of epilepsy have been hypothesized from the time of Hippocrates, the advent of new genetic technologies has played a tremendous role in elucidating a growing number of specific genetic causes for the epilepsies. This progress has contributed vastly to our recognition of the epilepsies as a diverse group of disorders, the genetic mechanisms of which are heterogeneous. Genotype-phenotype correlation, however, is not always clear. Nonetheless, the developments in genetic diagnosis raise the promise of a future of personalized medicine. Multiple genetic tests are now available, but there is no one test for all possible genetic mutations, and the balance between cost and benefit must be weighed. A genetic diagnosis, however, can provide valuable information regarding comorbidities, prognosis, and even treatment, as well as allow for genetic counseling. In this review, we will discuss the genetic mechanisms of the epilepsies as well as the specifics of particular genetic epilepsy syndromes. We will include an overview of the available genetic testing methods, the application of clinical knowledge into the selection of genetic testing, genotype-phenotype correlations of epileptic disorders, and therapeutic advances as well as a discussion of the importance of genetic counseling.

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Genetic testing in the epilepsies—developments and dilemmas

Cited by 70 publications

References 63 publications

HCN1 Gain-Of-Function Mutations – a New Cause of Epileptic Encephalopathy

HCN1 Gain-Of-Function Mutations – a New Cause of Epileptic Encephalopathy

Evidence-Based Pharmacotherapy of Epilepsy

The Genetics of the Epilepsies

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