Multidisciplinary Evaluation and a Genome-wide Analysis in a Cohort of Idiopathic Short Stature Patients

NCT05858606 | Recruiting

• 1 other identifier: RECHMPL22_0396
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Idiopathic Short Stature

Keywords

idiopathic short stature; whole genome analysis; monogenic conditions; syndromic disorders; skeletal dysplasia

Outcome Measures

Primary Outcomes (1)

• proportion of patients with authentified idiopathic short stature after multidisciplinary clinical-radiological analysis

  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

Secondary Outcomes (8)

• Genome positivity rate

  3 years

• Rate of positivity of molecular analyses prescribed as part of the care following the PCR

  3 years

• Rate of modification of management by the results of genome analysis

  3 years

• Type of change in management due to genome analysis results

  3 years

• Rate of change in management by results of molecular analysis

  3 years

Study Arms (1)

200 patients with idiopathic short stature,

EXPERIMENTAL

200 patients with apparently idiopathic short stature,

Diagnostic Test: Evaluation of the prevalence of truly (authentified) idiopathic short stature after multidisciplinary clinico-radiological evaluation; Procedure: analysis in a multidisciplinary consultation meeting via a secure platform (ShareConfrère) for evaluation by multidisciplinary team; Genetic: Whole genome analysis for authentified idiopathic short stature

Interventions

Evaluation of the prevalence of truly (authentified) idiopathic short stature after multidisciplinary clinico-radiological evaluation DIAGNOSTIC_TEST

1. pre-inclusion consultation 2. inclusion consultation * personal history * height, weight, cranial perimeters, and spans of both parents * clinical examination of the child * photographs of the child * additional X-rays

200 patients with idiopathic short stature,

analysis in a multidisciplinary consultation meeting via a secure platform (ShareConfrère) for evaluation by multidisciplinary team PROCEDURE

multidisciplinary team (geneticist, orthopedist, radiologist, pediatric endocrinologist) which will assign each patient an orientation: * either to the non idiopathic short stature group (syndromic diagnostic orientation or to a constitutional bone pathology) * or to the authentified idiopathic short stature group

200 patients with idiopathic short stature,

Whole genome analysis for authentified idiopathic short stature GENETIC

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.

200 patients with idiopathic short stature,

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children aged 4 to 18 years
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Service de Génétique Médicale - Arnaud de Villeneuve

Montpellier, 34295, France

RECRUITING

MeSH Terms

Conditions

Mucopolysaccharidosis IV

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Marjorlaine WILLEMS, MD

CONTACT

+33467336367; m-willems@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2023
• First Posted: May 15, 2023
• Study Start: March 16, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

FR (1)