Multidisciplinary evaluation and whole-genome testing for children with unexplained short stature
Pilot Study of Ethiology Research by a Multidisciplinary Evaluation Then a Genome-wide Analysis in a Cohort of Idiopathic Short Stature Patients
NA · University Hospital, Montpellier · NCT05858606
We will try whole-genome sequencing plus a team-based clinical review to find genetic causes of unexplained short stature in children aged 4–18.
Quick facts
| Phase | NA |
|---|---|
| Study type | Interventional |
| Enrollment | 200 (estimated) |
| Ages | 4 Years to 18 Years |
| Sex | All |
| Sponsor | University Hospital, Montpellier (other) |
| Locations | 1 site (Montpellier) |
| Trial ID | NCT05858606 on ClinicalTrials.gov |
What this trial studies
The project uses a two-step approach: first a standardized multidisciplinary clinico-radiological review to confirm truly idiopathic short stature after excluding common pediatric and endocrine causes, and then whole-genome sequencing for the first 30 confirmed cases. Eligible children have height below -2.5 SD (or below -2 SD of parental target height), normal basic laboratory and endocrine testing, and normal karyotype with FISH SHOX for girls. Imaging (spine, pelvis, limbs, hands/feet) and standardized photographs are collected, and cases are discussed via a secure multidisciplinary platform. The aim is to standardize diagnostic workup and determine how often monogenic causes explain apparently isolated short stature.
Who should consider this trial
Good fit: Children aged 4–18 with persistent short stature (height < -2.5 SD or < -2 SD of parental target), normal routine pediatric/endocrine workup, normal karyotype and girls with FISH SHOX performed, whose families consent to imaging and genetic testing.
Not a fit: Children with clear syndromic features, known skeletal dysplasia, abnormal basic laboratory or endocrine results, or those unable or unwilling to attend Montpellier visits or provide samples are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could identify genetic causes for some children, enabling more precise diagnoses, tailored management and informed genetic counseling.
How similar studies have performed: Previous next-generation sequencing studies have found genetic variants in subsets of short stature patients, but few have focused strictly on authentic idiopathic short stature without syndromic or skeletal signs, so this focused approach is partly novel.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Montpellier
- Service de Génétique Médicale - Arnaud de Villeneuve — Montpellier, France (RECRUITING)
Study contacts
- Study coordinator: Marjorlaine WILLEMS, MD
- Email: m-willems@chu-montpellier.fr
- Phone: +33467336367
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Idiopathic Short Stature, idiopathic short stature, whole genome analysis, monogenic conditions, syndromic disorders, skeletal dysplasia