Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new
            <i>CACNA1A</i>
            mutation

Kors, Esther E.; Melberg, Atle; Vanmolkot, Kaate R J; Kumlien, Eva; Haan, Joost; Raininko, Raili; Flink, Roland; Ginjaar, H.B.; Frants, Rune R.; Ferrari, Michel D.; Maagdenberg, Arn M. J. M. van den

doi:10.1212/01.wnl.0000138571.48593.fc

Cited by 103 publications

(81 citation statements)

References 7 publications

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“…Mutations in the CACNA1A gene (MIM 601011) have been reported in association with epilepsy and status epilepticus [26][27][28] and its haploinsufficiency has been suggested to be responsible for epilepsy and infantile spasms in the case of Auvin et al, 5 as well as for the abnormal electroencephalography in the case of Lysy et al 4 CACNA1A deletion is most likely responsible for the spontaneous focal seizures in case 3, whereas a positional effect concomitant to antipsychotic treatment might have evoked the epileptic seizure observed in case 1.…”

Section: Discussionmentioning

confidence: 99%

Genotype–phenotype relationship in three cases with overlapping 19p13.12 microdeletions

et al. 2010

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We describe the detailed clinical and molecular characterization of three patients (aged 7, 8 4/12 and 31 years) with overlapping microdeletions in 19p13.12, extending to 19p13.13 in two cases. The patients share the following clinical features with a recently reported 10-year-old girl with a 19p13.12 microdeletion: mental retardation (MR), psychomotor and language delay, hearing impairment, brachycephaly, anteverted nares and ear malformations. All patients share a 359-kb deleted region in 19p13.12 harboring six genes (LPHN1, DDX39, CD97, PKN1, PTGER1 and GIPC1), several of which may be MR candidates because of their function and expression pattern. LPHN1 and PKN1 are the most appealing; LPHN1 for its interaction with Shank family proteins, and PKN1 because it is involved in a variety of functions in neurons, including cytoskeletal organization. Haploinsufficiency of GIPC1 may contribute to hearing impairment for its interaction with myosin VI. A behavioral phenotype was observed in all three patients; it was characterized by overactive disorder associated with MR and stereotyped movements (ICD10) in one patient and hyperactivity in the other two. As Ptger1-null mice show behavioral inhibition and impulsive aggression with defective social interaction, PTGER1 haploinsufficiency may be responsible for the behavioral traits observed in these patients.

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Section: Discussionmentioning

confidence: 99%

Genotype–phenotype relationship in three cases with overlapping 19p13.12 microdeletions

et al. 2010

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“…Finally, several mutations in FHM1, a severe variant of migraine with aura associated with hemimotor/ sensory disturbance, are also associated with epilepsy, which can occur both in the setting of an attack and also separate to it (Ducros et al 2001;Beauvais et al 2004;Kors et al 2004;Zangaladze et al 2010;Chan et al 2008), although, generally, the association is markedly less than with EA2 in keeping with its underlying gain-of-function pathophysiology (van den Maagdenberg et al 2004).…”

Section: Dominant Mutations In Ca V 21 Cause Episodic Ataxia Type 2 mentioning

confidence: 99%

The Role of Calcium Channels in Epilepsy

Rajakulendran

Hanna

2016

Cold Spring Harb Perspect Med

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A central theme in the quest to unravel the genetic basis of epilepsy has been the effort to elucidate the roles played by inherited defects in ion channels. The ubiquitous expression of voltage-gated calcium channels (VGCCs) throughout the central nervous system (CNS), along with their involvement in fundamental processes, such as neuronal excitability and synaptic transmission, has made them attractive candidates. Recent insights provided by the identification of mutations in the P/Q-type calcium channel in humans and rodents with epilepsy and the finding of thalamic T-type calcium channel dysfunction in the absence of seizures have raised expectations of a causal role of calcium channels in the polygenic inheritance of idiopathic epilepsy. In this review, we consider how genetic variation in neuronal VGCCs may influence the development of epilepsy.

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“…Both migraine and epilepsy have an important genetic component, with strong evidence pointing to a shared genetic basis between headache and epilepsy emerging from clinical/EEG and genetic studies on Familial Hemiplegic Migraine (FHM) (Haglund and Schwartzkroin 1990;De Fusco et al 2003;Vanmolkot et al 2003;Kors et al 2004;Dichgans et al 2005;De Vries et al 2009;Tottene et al 2009Tottene et al , 2011Gambardella and Marini 2009;Van Den Maagdenberg et al 2010;Riant et al 2010;Pietrobon 2010;Uchitel et al 2012). Errors in the same gene may be associated with migraine in some cases and with epilepsy in others.…”

Section: Common Pathways Substrates and Geneticsmentioning

confidence: 99%

The Complex Relationship Between Epilepsy and Headache and the Concept of Ictal Epileptic Headache

Parisi

2014

Contemporary Clinical Neuroscience

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Key Points-Headache/migraine is often associated with epilepsy in children, as a pre-ictal, ictal, post-ictal or inter-ictal phenomenon.-Epidemiological aspects of the co-morbidity between epilepsy and headache are clearly different in children and adults.-Headache as a symptom, with migraine characteristics and/or tension-type headache characteristics, may be the only clinical ictal manifestation of an epileptic seizure: this condition is now classified as "ictal epileptic headache".-In particular, according to published criteria, the term "ictal epileptic headache" must be used in cases of a headache/migraine attack as the sole clinical ictal symptom of epileptic origin, confirmed by ictal-EEG recording and clinical-EEG responsiveness to intravenous antiepileptic drugs.-EEG is not recommended as a routine examination for children diagnosed with headache, but is mandatory and must be carried out promptly in cases of prolonged migraine/headache that does not respond to antimigraine drugs and in which epilepsy is suspected.-This is not a marginal question, because these possible, isolated, non-motor, ictal manifestations (i.e. ictal epileptic headache) should be taken into account before declaring an epileptic patient as "seizure free" so as to be able to suspend anticonvulsant therapy safely. SummaryThe possible link/comorbidity (causal or not causal) between epilepsy and headaches has been a topic of debate for over a hundred years, ever Since William Richard Gowers's time. In recent decades, new data have emerged in favor of a non-random relationship between these two entities. They are both characterized by transient attacks of altered brain function with a clinical, pathophysiological, genetic and therapeutic overlap, and may thus mimic each other. Indeed, the clinical distinction between headache and epilepsy may make the differential diagnosis a highly challenging task. Both are common and often co-morbid, with headache attacks in epilepsy being temporally related to the occurrence of epileptic seizures as a pre-ictal, ictal, post-ictal or inter-ictal event. Yet, they are both paroxysmal and chronic neurological disorders that share many clinical and epidemiological aspects, and they may both present with visual, cognitive, sensitive-sensorial and motor signs/symptoms; these neurophysiologicl phenomena arise from the cerebral cortex and are modulated by sub-cortical connections. Even from an epidemiological point of view, data in the literature regarding the co-morbidity between headache and epilepsy appear to be quite distinct in children. What makes this scenario even more variegated and complex are new data suggesting that a headache may, in some cases, even be the only ictal manifestation of an epileptic seizure. The latter condition, the so-called "ictal epileptic headache", is a new entity that has recently been cited in the new classification of headache disorders (ICHD-III), whose diagnostic criteria have very recently been defined and published. The data that have led, over the last decade, to the...

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Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation

Cited by 103 publications

References 7 publications

Genotype–phenotype relationship in three cases with overlapping 19p13.12 microdeletions

Genotype–phenotype relationship in three cases with overlapping 19p13.12 microdeletions

The Role of Calcium Channels in Epilepsy

The Complex Relationship Between Epilepsy and Headache and the Concept of Ictal Epileptic Headache

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