MALFORMATIONS OF CORTICAL DEVELOPMENT ? NEUROLOGICAL, EEG, MRI AND GENETIC CHARACTERISTICS

Project: Other project

Project Details

Description

Malformations of cortical development (MCDs) are a group of birth defects caused by abnormal migration of neurons in the developing brain and nervous system. This can result in brain malformation, cognitive dysfunction and epilepsy. Some examples of neuronal migration disorders include lissencephaly, schizencephaly, porencephaly, pachygyria, agyria, macrogyria, microgyria, neuronal heterotopia, agenesis of corpus callosum, agenesis of cranial nerves and band heterotopias. Cortical malformations are most often associated with mental retardation, epilepsy, and other sensory and motor deficiencies. Epilepsy occurs in 80 % of patients with cortical malformations, and MCDs are the reason for intractable seizures in about 20 ? 40 % of children ( Possi Y et al, 2012 ). The primary aim of this study is to identify children with MCDs attending Sultan Qaboos University Hospital and Royal hospital and delineate their clinical and molecular phenotype. The design of the study is retrospective with estimation of including 150 patients according to our current databases. We will include children between 0-18 years of age who attended SQUH and RH between 1/1/2007-31/12/2017. The study will focus on accomplishing three aims. 1. MRI identification of MCD: When classifying our patients with MCD; we aim to follow the international classifications (Barkovich et al 2001, Barkovich et al. 2005, Kuzniecky 1994) . All MRI of patients will be reviewed and classified by the radiologist in the study. Aim 2: Profile of neurological manifestations, epilepsy and EEG characteristics of different types of MCDs. To delineate the clinical features of patients with MCDs and to correlate between the type of MCDs and the severity of neurological manifestations. To characterize epilepsy and EEG findings and the ability to control seizures with medications versus intractable seizures in certain types of MCDs. Clinical data will be collected and all EEGs will be reviewed by the neurologist. Aim 3 Genetic profiles of MCD and its implication for severity of clinical phenotype in a term of neurological abnormality and epilepsy control. Upon retrospective chart review, the genetic testing will be collected for the included patients. If a patient has had a negative result (no abnormality detected) or did not have genetic testing yet, Whole Exome Sequencing (WES) will be offered. WES will have the advantage to cover all 20,000 coding genes and provide copy number variations. The team will be working on clinical data collection and classification of MCD During the first year and the genetic tests and analysis on the potential patients will be carried out during the second year. Given the patients numbers, high rate of consanguinity in Oman and unique ethnic background, this study aims to add to the understanding of such rare disorders and further study may be carried out later to better delineate the pathogenesis of MCDs.

Layman's description

Malformations of cortical development (MCDs) are a group of birth defects caused by abnormal migration of neurons in the developing brain and nervous system. This can result in brain malformation, cognitive dysfunction and epilepsy. Some examples of neuronal migration disorders include lissencephaly, schizencephaly, porencephaly, pachygyria, agyria, macrogyria, microgyria, neuronal heterotopia, agenesis of corpus callosum, agenesis of cranial nerves and band heterotopias. Cortical malformations are most often associated with mental retardation, epilepsy, and other sensory and motor deficiencies. Epilepsy occurs in 80 % of patients with cortical malformations, and MCDs are the reason for intractable seizures in about 20 ? 40 % of children ( Possi Y et al, 2012 ). The primary aim of this study is to identify children with MCDs attending Sultan Qaboos University Hospital and Royal hospital and delineate their clinical and molecular phenotype. The design of the study is retrospective with estimation of including 150 patients according to our current databases. We will include children between 0-18 years of age who attended SQUH and RH between 1/1/2007-31/12/2017. The study will focus on accomplishing three aims. 1. MRI identification of MCD: When classifying our patients with MCD; we aim to follow the international classifications (Barkovich et al 2001, Barkovich et al. 2005, Kuzniecky 1994) . All MRI of patients will be reviewed and classified by the radiologist in the study. Aim 2: Profile of neurological manifestations, epilepsy and EEG characteristics of different types of MCDs. To delineate the clinical features of patients with MCDs and to correlate between the type of MCDs and the severity of neurological manifestations. To characterize epilepsy and EEG findings and the ability to control seizures with medications versus intractable seizures in certain types of MCDs. Clinical data will be collected and all EEGs will be reviewed by the neurologist. Aim 3 Genetic profiles of MCD and its implication for severity of clinical phenotype in a term of neurological abnormality and epilepsy control. Upon retrospective chart review, the genetic testing will be collected for the included patients. If a patient has had a negative result (no abnormality detected) or did not have genetic testing yet, Whole Exome Sequencing (WES) will be offered. WES will have the advantage to cover all 20,000 coding genes and provide copy number variations. The team will be working on clinical data collection and classification of MCD During the first year and the genetic tests and analysis on the potential patients will be carried out during the second year. Given the patients numbers, high rate of consanguinity in Oman and unique ethnic background, this study aims to add to the understanding of such rare disorders and further study may be carried out later to better delineate the pathogenesis of MCDs.
AcronymTTotP
StatusNot started

Keywords

  • malformation of cortical development
  • developmental and genetic classification
  • epilepsy
  • malformation of cerebral cortex,
  • tuberous sclerosis complex

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