Progressive myoclonic epilepsies

Franceschetti, Silvana; Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; Neve, Angela La; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, G.; Tassinari, C. A.; Bianchi, Amedeo; Zara, Federico

doi:10.1212/wnl.0000000000000077

Cited by 91 publications

(84 citation statements)

References 31 publications

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“…For example, Unverricht-Lundborg disease (MIM 254800), the most common PME, is caused by AR mutations in CSTB (MIM 601145) 8–10 , the gene encoding cystatin B. In contrast, Lafora disease (MIM 254780), another form of PME, is caused by AR mutations in EPM2A (MIM 607566) and NHLRC1 (MIM 608072), the genes encoding laforin and malin, respectively 5; 11; 12 . Thus, although the genetic bases for several PMEs are known, additional genes remain to be identified for a substantial number of other cases 5 .…”

Section: Introductionmentioning

confidence: 99%

GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant

Giddens

Wong

Schroeder

et al. 2017

Neurobiology of Disease

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Progressive myoclonus epilepsies (PMEs) are disorders characterized by myoclonic and generalized seizures with progressive neurological deterioration. While several genetic causes for PMEs have been identified, the underlying causes remain unknown for a substantial portion of cases. Here we describe several affected individuals from a large, consanguineous family presenting with a novel PME in which symptoms begin in adolescence and result in death by early adulthood. Whole exome analyses revealed that affected individuals have a homozygous variant in GPR37L1 (c.1047G>T [Lys349Asp]), an orphan G protein-coupled receptor (GPCR) expressed predominantly in the brain. In vitro studies demonstrated that the K349N substitution in GPR37L1 did not grossly alter receptor expression, surface trafficking or constitutive signaling in transfected cells. However, in vivo studies revealed that a complete loss of Gpr37L1 function in mice results in increased seizure susceptibility. Mice lacking the related receptor Gpr37 also exhibited an increase in seizure susceptibility, while genetic deletion of both receptors resulted in an even more dramatic increase in vulnerability to seizures. These findings provide evidence linking GPR37L1 and GPR37 to seizure etiology and demonstrate an association between a GPR37L1 variant and a novel progressive myoclonus epilepsy.

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Section: Introductionmentioning

confidence: 99%

GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant

Giddens

Wong

Schroeder

et al. 2017

Neurobiology of Disease

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“…In many cases, even with such investigations, a specific etiologic diagnosis is not made. 4,5 In this case, despite extensive initial investigation, and exclusion of the commonly associated PME disorders, molecular diagnosis remained elusive until exome sequencing identified a SERPINI1 mutation, a rare cause of PME. Similarly, advances in next-generation sequencing have clarified the genes responsible for several novel PMEs 3 (table e-3) and will likely lead to earlier diagnoses in the future, obviating the need for protracted or irrelevant neurometabolic and single gene investigations.…”

Section: Go To Sectionmentioning

confidence: 98%

Clinical Reasoning: Juvenile neurocognitive decline

Allen¹,

Shahwan

Madigan³

et al. 2015

Neurology

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“…In these conditions, it can be hypothesized that the photoparoxysmal responses cannot be considered ''functional'' and transient events but are due to a more structured change in circuitry similar to that inducing persistent and often drug-resistant photoparoxysmal responses in adolescent or adult patients with progressive myoclonic epilepsies. 4 …”

Section: The Peculiarity Of Infantile Photoparoxysmal Responsesmentioning

confidence: 99%

Electroencephalographic (EEG) Photoparoxysmal Responses Under 5 Years of Age

et al. 2015

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Electroencephalographic (EEG) photoparoxysmal response has been little investigated in very young patients. We studied 5055 patients aged less than 5 years with no acquired brain damage, who underwent EEG recording. We determined the prevalence and significance of photoparoxysmal response induced by 1 to 20 Hz photic stimulation. Fifty-three showed photoparoxysmal response and were diagnosed as having Dravet syndrome (11), epileptic encephalopathy with myoclonic seizures (8), neurodegenerative disorders (8), benign idiopathic epilepsies (9), and static disorders with a known or suspected genetic origin (17). Photoparoxysmal response occurred in response to 1 to 5 Hz trains in 41.5% subjects. In most patients with epileptic encephalopathies, photoparoxysmal response was a transient finding: in 53.2%, it failed to be replicated in the recordings performed more than 6 months after initial evaluation. Photoparoxysmal response is rare in patients aged less than 5 years and has some peculiarities such as occurrence with low-frequency stimuli. Its distribution in specific conditions indicates that photoparoxysmal response may be useful in diagnostic workup.

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Progressive myoclonic epilepsies

Cited by 91 publications

References 31 publications

GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant

GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant

Clinical Reasoning: Juvenile neurocognitive decline

Electroencephalographic (EEG) Photoparoxysmal Responses Under 5 Years of Age

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