Pilot Study of Ethiology Research by a Multidisciplinary Evaluation Then a Genome-wide Analysis in a Cohort of Idiopathic Short Stature Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- proportion of patients with authentified idiopathic short stature after multidisciplinary clinical-radiological analysis
研究概览
简要总结
This trial aims to evaluate the prevalence of idiopathic short stature among children whose growth is above -2,5SD (AFPA- CRESS/Inserm -CompuGroup Medical 2018 curve) or above -2SD of the parental target size (taking child gender into account), after exclusion of classical pediatric and endocrinologic pathologies, and to evaluate the prevalence of monogenic causes of idiopathic short stature. A two-step study will be performed. The first one consists in a standardized multidisciplinary clinico-radiological evaluation of those children to evaluate the real prevalence of idiopathic short stature (ISS) among these patients. The second step consists in performing a whole genome sequencing analysis in the 30 first patients for whom the diagnosis of ISS is confirmed.
详细描述
Detailed description: Establishing the etiological diagnosis of short stature is an important step to guide the therapeutic management of patients and to propose appropriate genetic counseling. Short stature can be a symptom of many pathologies. However, in the majority of cases (80%), no specific etiology is found during a pediatric clinical investigation. In this case, the diagnosis of "idiopathic" short stature is performed. However, the diagnostic and therapeutic management of short stature after exclusion of classical pediatric causes is extremely heterogeneous and there are currently no consensual recommendations. A substantially higher proportion of diagnosed patients is therefore expected, along with more standardized clinical and genetic procedures. Additionally, in recent years, new methods of genetic investigation (gene panel, whole exome or whole genome sequencing analysis) have made it possible to identify many genetic variants associated with apparently isolated short stature. So far, none of the publications reporting next-generation sequencing analysis have focused on patients with authentic idiopathic short stature, i.e. without associated bone anomalies or syndromic features, and are often focused on only a subset of target genes.
This trial aims at estimating the prevalence of idiopathic short stature among children whose growth is above -2,5SD (AFPA- CRESS/Inserm -CompuGroup Medical 2018 curve) or above -2SD of the parental target size, after exclusion of classical pediatric and endocrinologic pathologies, and to evaluate the prevalence of monogenic causes of idiopathic short stature. A two-step study will be performed. The first one consists in a multidisciplinary clinico-radiological evaluation of those children to evaluate the real prevalence of idiopathic short stature (ISS) among these patients. The second step consists in performing a whole genome sequencing analysis in the 30 first patients for whom the diagnosis of authentic ISS is confirmed.
All patients will have:
- a pre-inclusion visit
- an inclusion visit after which the multidisciplinary clinico-radiological evaluation will be held
This analysis will assign patients to the diagnosis of either:
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
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 4 to 18 years
- •Height less than -2.5DS (standard deviations of the AFPA- CRESS/Inserm -CompuGroup Medical 2018 curve) or less than -2DS of the TCP (parental target height, corresponding to the average of parental heights +6.5 cm in boys, -6.5 cm in girls)
- •Normal karyotype + FISH SHOX for girls
- •Previously performed:celiac disease antibodies, WBC-platelets, CRP, blood ionogram, creatinine, blood calcium, blood phosphorus, ASAT, ALAT, PAL, PTH, TSH, T4L, growth hormone test normal according to the standards of the laboratory of the CHU of Montpellier
- •Acceptance of X-rays, in addition to those already performed as part of the care, which will not be repeated if necessary: spine front and profile, pelvis front, 1 upper limb front, 1 lower limb front F, hands and feet front
- •Acceptance of photographs: whole body with underwear, face face and profile, 2 faces of hands; feet, face
- •Acceptance of blood samples for the child and the 2 parents (trio)
- •Consent signed by both parents
排除标准
- •Intellectual disability (IQ below 70)
- •Cardiac, renal, digestive or cerebral malformation, cleft lip or palate, hearing or visual impairment, epilepsy
- •Renal or cardiac insufficiency, digestive or chronic inflammatory pathology
- •Previously established genetic diagnosis
研究组 & 干预措施
200 patients with idiopathic short stature,
200 patients with apparently idiopathic short stature,
干预措施: Evaluation of the prevalence of truly (authentified) idiopathic short stature after multidisciplinary clinico-radiological evaluation (Diagnostic Test)
200 patients with idiopathic short stature,
200 patients with apparently idiopathic short stature,
干预措施: analysis in a multidisciplinary consultation meeting via a secure platform (ShareConfrère) for evaluation by multidisciplinary team (Procedure)
200 patients with idiopathic short stature,
200 patients with apparently idiopathic short stature,
干预措施: Whole genome analysis for authentified idiopathic short stature (Genetic)
结局指标
主要结局
proportion of patients with authentified idiopathic short stature after multidisciplinary clinical-radiological analysis
时间窗: 3 years
Primary endpoint: The primary outcome is the proportion of patients with authentified idiopathic short stature after multidisciplinary clinical-radiological analysis (including geneticist, orthopedist, pediatric endocrinologist, radiologist) performed during a dedicated Multidisciplinary Consultation Meeting (MCM)
次要结局
- Variants within the same gene identified in at least 2 patients by whole genome analysis in the group of 30 patients with authentified idiopathic short stature in whom genome analysis has been performed(3 years)
- Rate of positivity of molecular analyses prescribed as part of the care following the PCR(3 years)
- Type of change in management due to genome analysis results(3 years)
- Type of management modification by molecular analysis resultscare context for those with non-idiopathic short stature(3 years)
- Rate of modification of management by the results of genome analysis(3 years)
- Rate of change in management by results of molecular analysis performed in a patient-care context for those with non-idiopathic short stature(3 years)
- Parental satisfaction assessed via a visual analog scale (Teleconsultation (1) and (2))(3 years)
- Genome positivity rate(3 years)
- Rate of change in management by results of molecular analysis(3 years)
- Parental satisfaction(3 years)
- Variants within the same gene identified in at least 2 patients by whole genome analysis(3 years)