Phenotypic Description of Patients With Atypical Clinical Forms of PLA2G6 Mutations
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 20
- 试验地点
- 7
- 主要终点
- Birth term in gestational weeks
研究概览
简要总结
Mutations in the PLA2G6 gene are well known in the classical phenotype called infantile neuro-axonal dystrophy (INAD), a severe neurodegenerative disease starting in infancy with homogeneous clinical, radiological, electrophysiological and pathophysiological features, with early death. Other clinical forms in pediatric patients called atypic INAD have been described in some patients. Expansion of high-throughput sequencing in the last decades has lead to identify mutations in the PLA2G6 gene in pediatric patients with late-onset phenotypes associating progressive ataxia, spastic paraplegia, cognitive regression and/or dystonia / parkinsonism. A high variability in radiological and electrophysiological findings is also described. Less than twenty patients with a pediatric onset have been reported with an atypical INAD. Very poor data are available on management and therapeutic options in these patients and global prognostic is not known. This multicentric retrospective study will record clinical, radiological, electrophysiological and pathophysiological data in pediatric patients with genetically confirmed atypical INAD. Management, therapeutics and evolution of the disease will also be recorded.
详细描述
Patients with biallelic mutations in PLA2G6 with an atypic INAD starting before 18 years will be recruited after a collaboration call of neuropaediatricians in France. After family consent, a retrospective collection of data will be performed using REDCap® digital questionnaire performed by the practitioner who follows / followed each patient.
Genetical, clinical, radiological, electrophysiological, pathophysiological outcomes will be anonymously recorded. Therapeutics proposed to patients, potential complications of the disease or treatments, age of premature death will also be recorded.
Data will be computed numerically and analysed in the Clermont-Ferrand center. A descriptive analysis will be proposed as the expected number of patients affected by this rare disease varies from 10 to 30. Median []interquartiles], means [standard deviation] and percentages will be calculated for quantitative data.
Collected data will include :
- general information :
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children with atypical neuroaxonal dystrophy under 18 years at disease-onset
- •with 2 deleterious mutations in the PLA2G6 gene
- •alive or deceased
- •Non-opposition of parents to participate to the retrospective study
排除标准
- •Classical form of infantile neuroaxonal dystrophy
- •Neuro-axonal dystrophy with adult-onset
- •Opposition of parents to participate to the retrospective study
结局指标
主要结局
Birth term in gestational weeks
时间窗: through study completion, an average of 9 months
quantitative feature, number of gestational weeks
Age at walking in years and months
时间窗: through study completion, an average of 9 months
quantitative feature, age in years and months
Acquisition of fine motor skills
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No
Neurological regression
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type of regression (language, motor, social, hearing, visual)
Age at sitting in months
时间窗: through study completion, an average of 9 months
quantitative feature, age in months
Autistic troubles
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No
Progressivity of symptoms
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No
Seizures
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset
Intellectual deficiency
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of severity (mild, moderate, severe, profound)
Pyramidal signs
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type (spasticity, Babinski, hyperreflexia, other)
Age at first language in years and months
时间窗: through study completion, an average of 9 months
quantitative feature, age in years and months
Axial hypotonia
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No
Peripheral neurological signs
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type (myopathy, neuropathy, areflexia, bulbar signs, other)
Movement disorders
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type (dystonia, paroxysmal dyskinesia, parkinsonism, nystagmus, ataxia, other)
Radiological abnormalities
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type (Iron deposits, White matter abnormalities, Cerebellar atrophy, Optic nerve atrophy, Brainstem atrophy, Cortical-subcortical atrophy, Splenium verticalization, Other abnormalities of corpus callosum, Clava hypertrophy, Other)
Gastro-intestinal disorders
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type
Behavioral or mood disorders
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type
Sleep disorders
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type
Visual abnormalities
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type (strabism, nystagmus, eye fundus abnormalities, other)
GMFCS
时间窗: through study completion, an average of 9 months
GMFCS scoring from 1 to 5
Orthopaedic disorders
时间窗: through study completion, an average of 9 months
Qualitative feature, answer :Yes / No Precision of age at onset Precision of type (scoliosis, hip, ankle deformations, other)
次要结局
- Therapeutics(through study completion, an average of 9 months)
- Phenotype-genotype correlation(through study completion, an average of 9 months)
- Mutations in PLA2G6(through study completion, an average of 9 months)
- Electrophysiological findings(through study completion, an average of 9 months)
- Pathophysiological findings(through study completion, an average of 9 months)