특발성 저신장 환자 코호트에 대한 다학제적 평가 및 유전체 분석 (PAG PETI)
특발성 저신장 환자 코호트에서 다학제적 평가 후 게놈 차원 분석에 의한 병인학 연구의 파일럿 연구
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.
연구 개요
상태
정황
개입 / 치료
- 진단 검사: Evaluation of the prevalence of truly (authentified) idiopathic short stature after multidisciplinary clinico-radiological evaluation
- 절차: analysis in a multidisciplinary consultation meeting via a secure platform (ShareConfrère) for evaluation by multidisciplinary team
- 유전적: Whole genome analysis for authentified idiopathic short stature
상세 설명
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:
- non-idiopathic short stature (diagnosis of constitutional bone disease or syndromic disorder)
- authentic idiopathic short stature
A teleconsultation (1) to explain to the parents the conclusions of the multidisciplinary clinico-radiological evaluation.
This teleconsultation will be followed for all patients in the "non-idiopathic short stature" group, by a visit to take samples for genetic analysis in the context of clinical care, followed by a teleconsultation (2) to give them and explain the results
This teleconsultation will be followed for the first 30 patients in the "authentified idiopathic short stature" group, by a visit to take samples for whole genome analysis in the context of research, followed by a teleconsultation (2) to return the results.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Marjorlaine WILLEMS, MD
- 전화번호: +33467336367
- 이메일: m-willems@chu-montpellier.fr
연구 장소
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Le Kremlin-Bicêtre, 프랑스, 94270
- 모병
- Endocrinologie et Diabétologie pédiatrique - Hôpital Kremlin Bicêtre - APHP
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연락하다:
- Agnes LINGLART, MD
- 전화번호: +331 45 21 78 53
- 이메일: agnes.linglart@aphp.fr
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Lyon, 프랑스
- 모병
- HCL
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연락하다:
- Dr Carine Villanueva, MD
- 전화번호: +334 27 85 53 28
- 이메일: carine.villanueva@chu-lyon.fr
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Montpellier, 프랑스, 34295
- 모병
- Service de Génétique Médicale - Arnaud de Villeneuve
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연락하다:
- Marjolaine WILLEMS, MD
- 전화번호: +33467336367
- 이메일: m-willems@chu-montpellier.fr
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Toulouse, 프랑스, 31059
- 모병
- Unité d'Endocrinologie, Maladies Osseuses et Génétique - Hôpital des Enfants, CHU de Toulouse
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연락하다:
- Thomas EDOUARD, MD
- 전화번호: +335 34 55 85 55
- 이메일: edouard.t@chu-toulouse.fr
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Children aged 4 to 18 years
- 2 sexes
- 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
Exclusion Criteria:
- 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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 특수 증상
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 200 patients with idiopathic short stature,
200 patients with apparently idiopathic short stature, |
multidisciplinary team (geneticist, orthopedist, radiologist, pediatric endocrinologist) which will assign each patient an orientation:
For the first 30 patients included in the authentified idiopathic short stature group, a whole genome analysis in trio (child + parents) will be performed as part of the research. For these 30 patients in the authentified idiopathic short stature group, the teleconsultation carried out for the submission of the multidisciplinary consultation meeting conclusions will make it possible to establish the family tree, to explain the interest and limits of the analysis, and to submit the consents dedicated to the genetic analysis. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
proportion of patients with authentified idiopathic short stature after multidisciplinary clinical-radiological analysis
기간: 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) |
3 years
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Genome positivity rate
기간: 3 years
|
Genome positivity rate (positive diagnosis of pathogenic variation or probably pathogenic variation variants involved in the phenotype) in the group of 30 patients with authentified idiopathic short stature patients in whom the genome analysis was performed |
3 years
|
|
Rate of positivity of molecular analyses prescribed as part of the care following the PCR
기간: 3 years
|
Rate of positivity of molecular analyses prescribed as part of the care following the PCR (positive diagnosis of pathogenic or probably pathogenic variants involved in the phenotype) for patients with non-idiopathic short stature |
3 years
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Rate of modification of management by the results of genome analysis
기간: 3 years
|
Rate of modification of management by the results of genome analysis in the group of 30 patients with authentified idiopathic short stature in whom genome analysis has been performed |
3 years
|
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Type of change in management due to genome analysis results
기간: 3 years
|
Type of change in management due to genome analysis results: initiation/withdrawal of treatment, referral to organ specialist for specific multidisciplinary management (patients with authentified idiopathic short stature/ Genome+) |
3 years
|
|
Rate of change in management by results of molecular analysis
기간: 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
|
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Type of management modification by molecular analysis resultscare context for those with non-idiopathic short stature
기간: 3 years
|
Type of management modification by molecular analysis results: initiation/withdrawal of treatment, referral to organ specialist for specific multidisciplinary management (patients with non-idiopathic short stature). |
3 years
|
|
Parental satisfaction
기간: 3 years
|
Parental satisfaction will be assessed using a Visual Analog Scale (VAS) ranging from 0 to 10, where 0 indicates "not satisfied at all" and 10 indicates "completely satisfied." Higher scores indicate greater parental satisfaction. Assessments will be conducted following teleconsultations (Teleconsultation 1 and Teleconsultation 2). |
3 years
|
|
Variants within the same gene identified in at least 2 patients by whole genome analysis
기간: 3 years
|
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
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- RECHMPL22_0396
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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