Dataset Information

Epileptic spasms are a feature of DEPDC5 mTORopathy.

ABSTRACT:

Objective

To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms.

Methods

We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants.

Results

We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable.

Conclusions

While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies.

SUBMITTER: Carvill GL

PROVIDER: S-EPMC4807908 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Epileptic spasms are a feature of DEPDC5 mTORopathy.

Carvill Gemma L GL Crompton Douglas E DE Regan Brigid M BM McMahon Jacinta M JM Saykally Julia J Zemel Matthew M Schneider Amy L AL Dibbens Leanne L Howell Katherine B KB Mandelstam Simone S Leventer Richard J RJ Harvey A Simon AS Mullen Saul A SA Berkovic Samuel F SF Sullivan Joseph J Scheffer Ingrid E IE Mefford Heather C HC

Neurology. Genetics 20150723 2

<h4>Objective</h4>To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms.<h4>Methods</h4>We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants.<h4>Results</h4>We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epil ...[more]

PMID: 27066554

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Project description:ObjectiveAmong standard treatments for infantile spasms, adrenocorticotropic hormone (ACTH) is reported as the best treatment, but ACTH is ineffective in one-half of the patients. To establish precision medicine, we examined pharmacoresistance of focal epileptic spasms (ES), generalized ES, and generalized ES combined with focal seizures, diagnosed based on the revised seizure classification of ILAE in 2017.MethodsWe conducted a retrospective nationwide study in Japan on the long-term seizure outcome of ES. Long-term seizure outcome was evaluated by seizure-free rate, seizure-free period, and Kaplan-Meier curve. Seizure-free was defined as seizure control for longer than 2 months.ResultsFrom the medical history of 501 patients, 325 patients had generalized ES only (GES group) at the start of the first treatment, 125 patients had generalized ES after focal seizure onset (FS-GES group), seven patients had focal ES after focal seizure onset (FS-FES group), and 24 patients had generalized ES combined with focal seizures after focal seizure onset (FS-GES + FS group). Seizure-free period of ES (generalized ES and focal ES) [mean (95% confidence interval)] was 2.7 (0.0-5.4) months in GES group, 1.1 (0.1-2.2) months in FS-GES group, 1.0 (0.2-1.9) months in FS-GES + FS group, and 0.1 (-0.2-0.5) months in FS-FES group. Seizure-free rate, seizure-free period, and Kaplan-Meier curve of generalized ES were almost the same in GES group and FS-GES group, with characteristics of superior response to ACTH. Mean seizure-free period of generalized ES combined with focal seizures was significantly shorter in FS-GES + FS group than in GES group. Mean seizure-free period of focal ES in FS-FES group was extremely short with exceedingly early relapse.SignificancePharmacoresistance was different in generalized ES, focal ES, and generalized ES combined with focal seizures. ES with focal features or with focal seizures may have focal lesions, thus consider surgical options earlier in the course.

Project description:ObjectiveTo determine the structural networks that constrain propagation of ictal oscillations during epileptic spasm events, and compare the observed propagation patterns across patients with successful or unsuccessful surgical outcomes.MethodsSubdural electrode recordings of 18 young patients (age 1-11 years) were analyzed during epileptic spasm events to determine ictal networks and quantify the amplitude and onset time of ictal oscillations across the cortical surface. Corresponding structural networks were generated with diffusion magnetic resonance imaging (MRI) tractography by seeding the cortical region associated with the earliest average oscillation onset time, and white matter pathways connecting active electrode regions within the ictal network were isolated. Properties of this structural network were used to predict oscillation onset times and amplitudes, and this relationship was compared across patients who did and did not achieve seizure freedom following resective surgery.ResultsOnset propagation patterns were relatively consistent across each patient's spasm events. An electrode's average ictal oscillation onset latency was most significantly associated with the length of direct corticocortical tracts connecting to the area with the earliest average oscillation onset (p < .001, model R2 = .54). Moreover, patients demonstrating a faster propagation of ictal oscillation signals within the corticocortical network were more likely to have seizure recurrence following resective surgery (p = .039). In addition, ictal oscillation amplitude was associated with connecting tractography length and weighted fractional anisotropy (FA) measures along these pathways (p = .002/.030, model R2 = .31/.25). Characteristics of analogous corticothalamic pathways did not show significant associations with ictal oscillation onset latency or amplitude.SignificanceSpatiotemporal propagation patterns of high-frequency activity in epileptic spasms align with length and FA measures from onset-originating corticocortical pathways. Considering the data in this individualized framework may help inform surgical decision-making and expectations of surgical outcomes.

Dataset Information

Epileptic spasms are a feature of DEPDC5 mTORopathy.

Objective

Methods

Results

Conclusions

Publications

Epileptic spasms are a feature of DEPDC5 mTORopathy.

Similar Datasets

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