Phenotype and Genotype Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis. The Use of Genetic Analysis in the Early Care of Children With Thyroid Dysgenesis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 558
- 试验地点
- 2
- 主要终点
- etiological type of the congenital hypothyroidism
研究概览
简要总结
Congenital hypothyroidism (CH) is a rare disease that affects 1 in 3500 newborn. This condition is detected consistently since the late 1970s in France, which has led to early care and a significant improvement in prognosis and intellectual stature of these children. However neurodevelopmental disorders persist in 10-15% of cases. More associated diseases have been reported in approximately 10% of cases. These observations are in most cases poorly understood. The family nature of the CH is now well recognized and a dozen genes involved up to now. However, in the majority of cases (HC not due to a disorder of the organification of iodine), few mutations have been found in the reported number of patients (5-10%), suggesting the involvement of other genes. Some of the genes have been implicated in particular specific syndromic forms but many pathological associations remain unexplained. Also, a more complete genetic elucidation of CH would enable a better understanding of its etiology and thus its risk of familial recurrence (frequently asked questions by parents of children with CH) and secondly the presence of associated pathologies.
Main goal: to describe the population with CH (not due to a disorder of the organification of iodine) not only on clinical, biological and radiological (phenotypic analysis) but also on the genetic level to establish a genotype / phenotype correlation.
详细描述
Congenital hypothyroidism (CH) is a rare disease that affects 1 in 3500 newborn. This condition is detected consistently since the late 1970s in France, which has enabled early care and a significant improvement of the intellectual stature and prognosis of these children. However neurodevelopmental disorders persist in 10-15% of cases. More associated pathologies have been reported in nearly 10% of cases. These observations are in most cases poorly understood. The family nature of the HC is now well accepted and a dozen genes is now involved. However in the majority of cases (HC not due to a disorder of the organification of iodine), few mutations have been found relative to the number of patients (5-10%), suggesting the involvement of other genes. Some of the genes have been implicated in such specific syndromic forms but many pathological associations remain unexplained. Also, a more complete elucidation of genetic HC enable a better understanding of its etiology and thus share the risk of familial recurrence (frequently asked by parents of children with questions) and secondly the presence of comorbidities.
Main objective: To describe the population with HC (not due to a disorder of the organification of iodine) not only on clinical, biological and radiological (phenotypic analysis) but also at the genetic level to establish a genotype / phenotype correlation.
Secondary objectives:
- study the frequency of malformations and / or pathological associations in patients with HC
- identify groups of patients with syndromic forms in whom early treatment may improve the prognosis of children
- to search for mutations in genes known to be involved in the pathology
- to search for new loci and / or genes involved
- to determine the optimal genetic strategy to adopt before a HC case.
Inclusion criteria:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Patient: newborn (0-27 days) or infant (28 days 23 months), or child or adult with congenital hypothyroidism (that is to say with a TSH > 15 mU / ml at screening on filter paper and / or plasma TSH> 10 mU / ml) diagnosed in the first months of life, whatever their age, sex, weight and size.
- •Subjects with blood levels of free thyroid hormones (FT3 and FT4) in the standards will be described as having subclinical hypothyroidism.
- •If treatment with L-thyroxine could be stopped without relapse (that is to say, always with a TSH <5 mU / ml with different controls), hypothyroidism is said to be transient, whatever the age of discontinuation of treatment.
- •No pre or neonatal goitre by palpation or ultrasound thyroid
- •negative perchlorate test (ie decreased rate of iodine captation <10% at 2h injection of perchlorate) when the thyroid gland in place
- •No self-immunity known to thyroid in children with and / or his mother (defined by a antithyroperoxidase antibodies and / or antithyroglobulin)
- •Signature of free and informed consent by the patient or his legal representative
- •Affiliation or enjoying a social security system
排除标准
- •Presence of markers antithyroid autoimmunity in children and / or mother (antithyroperoxidase antibodies and / or antithyroglobulin)
- •Pre or neonatal goiter on palpation or ultrasound thyroid
- •Test positive perchlorate (ie salting rate of iodine> 10% at 2 injection perchlorate)
- •Patients of foreign origin returned to their country will be excluded from the study.
研究组 & 干预措施
hypothyroid group
Clinical exams radiologic exams Blood sample
干预措施: Clinical and radiologic exams and blood samples (Other)
结局指标
主要结局
etiological type of the congenital hypothyroidism
时间窗: 2 years
Etiological Type of the congenital hypothyroidism: athyreosis, ectopia, hémiagenesis, hypoplastic gland in place of normal shape and size
Presence and type of cytogenetic and / or genetic abnormality associated with HC
时间窗: 2 years
Presence and type of pathology associated with HC
时间窗: 2 years
Presence of abnormal neuropsychological (including delayed psychomotor development)
时间窗: 2 years
次要结局
- Presence of a prenatal and / or neonatal complication(2 years)
- time to treatment of hypothyroidism(2 years)