Study to Investigate Genetic Causes of Severe Early Childhood Onset Obesity.

Study Overview
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Brief Summary
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This study aims to investigate genetic causes of early childhood obesity. The investigators will enroll children and young adults with severe early onset obesity (BMI > 99th percentile) diagnosed prior to 6 years of age. The investigators will ask questions about the health and eating behavior of the participants, and perform a brief physical examination. The investigators will collect saliva or blood to perform genetic testing from the participants and invite family members to enroll in the study.

Detailed Description
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This is a clinical and genomic study designed to investigate monogenic causes of severe early childhood obesity. Participants with severe early onset obesity will be identified by screening of the clinical database or referred for the study. These subjects will be invited to participate in the study. After obtaining informed consent, the investigators will obtain history on the proband and the family, and perform a brief examination in addition to collecting genetic material. Targeted sequencing of genes associated with monogenic and syndromic forms of obesity will be performed using next-generation sequencing. In selected individuals with favorable family history, exome or whole genome sequencing will be performed. Functional analysis of newly identified variants will be performed where possible.

Official Title
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Study to Identify Rare Genetic Variants Causing Severe Early Childhood Obesity

Conditions
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Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - BMI > 99th percentile documented at age < 6 years of age Exclusion Criteria: Known genetic causes of obesity Known Endocrine causes of obesity. Neurologic tumor, trauma or surgery Prior malignancy or transplant Known autoimmune diseases Edema of a known or unknown cause Prolonged steroid use.

Ages Eligible for Study
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Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Early-onset severe obesity<br>The study will enroll children and young adults up to 21 years of age with early onset severe obesity (BMI > 99th percentile noted at an age < 6 years of age). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of known or novel genetic variants in genes that underlie obesity. | Identification of known or novel genetic variants in genes that underlie obesity. | 1.5-2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of melanocortin receptor 4 mutations. | We will test the hypothesis that 1-3% of early onset obesity could be explained by carriage of mutation of monogenic obesity such as melanocortin receptor 4 in a mixed pediatric population. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, genetics, early-onset, childhood