Genetic Investigations in Children With Developmental and Epileptic Encephalopathies in Ho Chi Minh City, Vietnam: A Collaborative, Prospective, Tertiary Care Center Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- The proportion of children with developmental and epileptic encephalopathies for whom advanced genetic investigations allow the identification of pathogenic gene variants
研究概览
简要总结
Early childhood is one of the periods of life in which the risk to develop epilepsy is highest. Besides, genetic causes are much more common in the young. Recently, an ever-increasing amount of genes has been found to be involved in numerous early-onset epilepsies. Thanks to next-generation sequencing (NGS), a diagnosis can now be reached in close to 50% of children with epilepsy and developmental delay. This, in turn, has led to the successful application of the concept of individualized treatment in a growing number of children with epilepsy. Genetic investigations have thus been progressively included in the routine work-up of children with early-onset epilepsies throughout the world, mostly in high-income countries up to now. As a result of a scientific collaboration between pediatric neurology divisions at University Hospitals Geneva (HUG), Switzerland, and Children's Hospital 2 in Ho Chi Minh City (HCMC), Viet Nam, genetic testing of children with early-onset epilepsies followed at the pediatric neurology division, Children's Hospital 2 started at the genetics laboratory of the Vietnam National University in 2017.
Aims: Our project aims at establishing the proportion of patients in whom a causal genetic finding can be identified, in a prospective cohort of children with Developmental and Epileptic Encephalopathies (DEE) followed at Children's Hospital 2 (ND2). The investigators also aim at identifying the percentage of these children in whom this approach would change current management.
Methods: A series of children diagnosed with DEE and followed at ND2 Hospital, enrolled consecutively. Exome sequencing was applied to all, with biostatistical analyses of a panel of 671 genes involved in epilepsies and developmental disorders performed in parallel at Ho Chi Minh City Vietnam National University and Geneva Genetic Medicine Division. Sanger sequencing confirmation of potentially causal variants in patients, and in parents for familial segregation. Comparison of Vietnamese and Swiss genetic findings, and multidisciplinary discussions in formal Genome Boards. Additional genetic investigations, if deemed necessary in Genome Board sessions. Clinical management adapted to genetic findings wherever applicable, and follow-up according to standard practice. One-hundred-and-fifty patients are expected to participate during the 3-year study period.
详细描述
With this prospective cohort study, the investigators wish to know the proportion of children with developmental and epileptic encephalopathies followed at the largest pediatric neurology facility in South Vietnam and enrolled consecutively for whom advanced genetic investigations allow the identification of pathogenic gene variants. The investigators expect this proportion to be 50%.
The investigators will also investigate the proportion of children in whom the genetic results will allow individualized treatment adaptations and global management changes. The investigators expect this proportion to be at least 10 %.
This collaborative project is the first step to demonstrating the clinical utility of high-throughput genetic procedures for all patients with severe early-onset epilepsy and developmental difficulties in Viet Nam. Parallel analyses of patients' exome sequences in Vietnam and Switzerland will allow the optimization of the procedure.
Patient selection:
Based on a birth rate of 16.745 children/1000 people in Vietnam (2018 statistics, data.worldbank.org, consulted Dec 18th, 2020), a mortality rate of 15.9/1'000 live births in Vietnam (2019 statistics, data.worldbank.org, consulted Dec 18th, 2020), a total of 1'394'401 live births in the entire country, and a nationwide population of 97'752'966 of which 8'602'317 live in HCMC (2020 statistics, worldometers.info, worldpopulationreview.org, consulted Dec 18th, 2020), the investigators estimate that 122'708 to 144'046 children are born in the city each year, of which 120'756 to 141'756 will stay alive. On the basis of a recently calculated general incidence of 54/100'000 live births in the State of Victoria, Australia, and a comparable age-adjusted incidence of 44.8/100'000 persons in Ba Vi, a rural district of Vietnam, the investigators estimate that 54-75 children with SEI are born every year in HCMC. Given the fact that a majority of these children are followed at ND2, and that many patients with severe neurological conditions coming from a broader area also consult at ND2, our aim is to enroll 50 children per year.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 3 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Drug-resistant epilepsy, either from onset, or at follow-up, according to ILAE 2010 criteria
- •Severe developmental delay or regression, according to paediatric neurologist evaluation (or developmental quotient <50, if formally assessed)
- •Age of onset of principal symptoms (Seizures, Developmental delay): 0-36 months
- •Agreement to take part in the study and signed consent form
排除标准
- •Patients with identified structural, infectious or inflammatory causes (such as perinatal hypoxic-ischemic encephalopathy, Cerebrovascular disorders, Sequelae of trauma or encephalitis, neurocutaneous disorders, etc...) will not be asked to take part to the study.
结局指标
主要结局
The proportion of children with developmental and epileptic encephalopathies for whom advanced genetic investigations allow the identification of pathogenic gene variants
时间窗: 36 months
the proportion of children with developmental and epileptic encephalopathies followed at the largest paediatric neurology facility in South Vietnam and enrolled consecutively for whom advanced genetic investigations allow the identification of pathogenic gene variants.
The proportion of children in whom the genetic results will allow individualized treatment adaptations
时间窗: 36 months
proportion of children in whom the genetic results will allow individualized treatment adaptations
次要结局
未报告次要终点
研究者
Thuy-Minh-Thu NGUYEN
Principal Investigator
Number 2 Children's Hospital, Ho Chi Minh City