Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome

Study Overview
=================
Brief Summary
-----------------
Introduction: Williams-Beuren syndrome is a rare genetic disorder caused by a 7q11.23 microdeletion. The phenotype associates vasculopathy (arterial stenosis, hypertension), dimorphism and intellectual disability. Microdeletion includes several genes: ELN encodes for elastin and the haplo-insufficiency (only 1 functional copy) causes vasculopathy. The primary objective is to quantify plasma and urinary levels of elastin peptides in Williams-Beuren patients and 7q11.23 micro-duplication syndrome patients in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship gene copy number - circulating levels of markers) Materials and Methods: This prospective study will be carried out in Lyon at the Hôpital Femme-Mère-Enfant for 2 years. 3 groups of patients will be studied: Williams-Beuren patients (N=20), micro-duplication 7q11.23 syndrome patients (N=10) and healthy patients (N=60). Subjects will be followed for 1 day. Clinical examination (weight, height, blood pressure) and biological sample collection (blood and urine sample) will be carry out for Williams Beuren and micro-duplication 7q11.23 patients group. A large majority of visits will be part of patients' usual care. A large part of patients are systematically seen in consultation once a year. For healthy group, only biological sample collection will be carry out. The PE concentrations will be assessed and compared between the three groups of patients.

Official Title
-----------------
Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome

Conditions
-----------------
Williams-Beuren Syndrome, Micro-duplication 7q11.23 Syndrome, Vasculopathy

Intervention / Treatment
-----------------
* Biological: Physical examination and Urine and blood samples
* Biological: Urine and blood samples


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age : from 3 months to 60 years old Williams Beuren group : Diagnosis confirmed with FISH Micro-duplication 7q11.23 group : Diagnosis confirmed with CGHarray Healthy Group : no cardiovascular and neurological medical history Informed consent Exclusion Criteria: No social insurance Subject under judicial protection Subject participating in another research including an exclusion period still in progress

Ages Eligible for Study
-----------------
Minimum Age: 3 Months
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Williams Beuren<br>Subjects aged from 3 months to 60 years with a diagnosis confirmed with FISH of Williams Beuren syndrome. | Biological: Physical examination and Urine and blood samples<br>* Only one visit for each participant : A large majority of visits will be part of patients' usual care Medical examination : birth, weight, gender, blood pressure, medical history Urine and blood samples<br>|
| Other: Micro-duplication 7q11.23<br>Subjects aged from 3 months to 60 years with a diagnosis confirmed with CGHarray of micro-duplication 7q11.23 syndrome. | Biological: Physical examination and Urine and blood samples<br>* Only one visit for each participant : A large majority of visits will be part of patients' usual care Medical examination : birth, weight, gender, blood pressure, medical history Urine and blood samples<br>|
| Other: Healthy Group<br>Subjects without cardiovascular and neurological medical history. | Biological: Urine and blood samples<br>* Only one visit for each participant Medical history Urine and blood samples<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma level of elastin peptides (PE) | To quantify plasma level of elastin peptides in participants in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship gene copy number - circulating levels of markers). The primary endpoint will be assessed by measuring the blood level of PE between groups | 1 day | 
| Urinary level of elastin peptides (PE) | To quantify urinary level of elastin peptides in participants in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship gene copy number - circulating levels of markers). The primary endpoint will be assessed by measuring the urinary level of PE between groups | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between blood level of PE and cardiovascular involvement in patients. | Blood level of PE will be correlated with the presence / severity of cardiovascular disease | 1 day | 
| Correlation between urinary level of PE and cardiovascular involvement in patients. | Urinary level of PE will be correlated with the presence / severity of cardiovascular disease | 1 day | 
| Blood level of PE in treated and untreated minoxidil patients | Blood levels of PE in the samples of patients who participated in the minoxidil clinical trial will be compare to those of participants of this study | 1 day | 
| Urinary level of PE in treated and untreated minoxidil patients | Urinary levels of PE in the samples of patients who participated in the minoxidil clinical trial will be compare to those of participants of this study | 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Williams-Beuren Syndrome, Micro-duplication 7q11.23 syndrome, Vasculopathy