5 research outputs found
L ennoxâ G astaut syndrome of unknown cause: Phenotypic characteristics of patients in the E pilepsy P henome/ G enome P roject
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101778/1/epi12395.pd
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Racial and ethnic differences in epilepsy classification among probands in the Epilepsy Phenome/Genome Project (EPGP)
Little is known about the ethnic and racial differences in the prevalence of generalized and focal epilepsy among patients with non-acquired epilepsies. In this study, we examined epilepsy classification and race/ethnicity in 813 probands from sibling or parent-child pairs with epilepsy enrolled in the Epilepsy Genome/Phenome Project (EPGP). Subjects were classified as generalized epilepsy (GE), non-acquired focal epilepsy (NAFE), mixed epilepsy syndrome (both generalized and focal), and unclassifiable, based on consensus review of semiology and available clinical, electrophysiology, and neuroimaging data. In this cohort, 628 (77.2%) subjects identified exclusively as Caucasian/white and 65 (8.0%) subjects reported African ancestry, including subjects of mixed-race. Of the Caucasian/white subjects, 357 (56.8%) had GE, 207 (33.0%) had NAFE, 32 (5.1%) had a mixed syndrome, and 32 (5.1%) were unclassifiable. Among subjects of African ancestry, 28 (43.1%) had GE, 27 (41.5%) had NAFE, 2 (3.1%) had a mixed syndrome, and 8 (12.3%) were unclassifiable. There was a higher proportion of subjects with GE compared to other syndromes among Caucasians/whites compared to subjects with African ancestry (OR 1.74, 95% CI: 1.04-2.92, two-tailed Fisher's exact test, p=0.036). There was no difference in the rate of GE among subjects reporting Hispanic ethnicity (7.6% of total) when adjusted for race (Caucasian/white vs non-Caucasian/white; OR 0.65, 95% CI: 0.40-1.06, p>0.05). The proportion of participants with unclassifiable epilepsy was significantly greater in those of African-American descent. In a group of patients with epilepsy of unknown etiology and an affected first degree relative, GE is more common among Caucasian/white subjects than among those with African ancestry. These findings suggest there may be geographical differences in the distribution of epilepsy susceptibility genes and an effect of genetic background on epilepsy phenotype. However, the results should be interpreted with caution because of the low numbers of African-Americans in this cohort and more limited diagnostic data available for epilepsy classification in these subjects compared to Caucasians/whites
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Familial aggregation of focal seizure semiology in the Epilepsy Phenome/Genome Project
ObjectiveTo improve phenotype definition in genetic studies of epilepsy, we assessed the familial aggregation of focal seizure types and of specific seizure symptoms within the focal epilepsies in families from the Epilepsy Phenome/Genome Project.MethodsWe studied 302 individuals with nonacquired focal epilepsy from 149 families. Familial aggregation was assessed by logistic regression analysis of relatives' traits (dependent variable) by probands' traits (independent variable), estimating the odds ratio for each symptom in a relative given presence vs absence of the symptom in the proband.ResultsIn families containing multiple individuals with nonacquired focal epilepsy, we found significant evidence for familial aggregation of ictal motor, autonomic, psychic, and aphasic symptoms. Within these categories, ictal whole body posturing, diaphoresis, dyspnea, fear/anxiety, and déjà vu/jamais vu showed significant familial aggregation. Focal seizure type aggregated as well, including complex partial, simple partial, and secondarily generalized tonic-clonic seizures.ConclusionOur results provide insight into genotype-phenotype correlation in the nonacquired focal epilepsies and a framework for identifying subgroups of patients likely to share susceptibility genes
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The epilepsy phenome/genome project.
BackgroundEpilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy.ResultsEPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants.ConclusionsEPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review