Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome
Study Details
Study Description
Brief Summary
Rapid onset Obesity, Hypoventilation, Hypothalamic dysfunction and Autonomic Dysregulation (ROHHAD) is a syndrome named in 2007. The hallmark of the syndrome is the rapid onset obesity and dysregulation of central ventilation. There is little information about the metabolic changes that lead to the rapid onset obesity in these children. The investigators would like to study the metabolic phenotype of these children to understand the disturbances in energy balance that lead to the rapid onset obesity.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Late-onset hypoventilation syndrome with hypothalamic dysfunction was first described in 1965 and renamed to ROHHAD syndrome in 2007 by Ize-Ludlow et al.
The hallmark of ROHHAD syndrome is rapid-onset obesity starting at approximately 1.5 years of age with weight gain of 12-20 kg/year, central hypoventilation distinct from the obstructive hypoventilation caused by obesity, hyperphagia, a spectrum of pituitary hormonal dysfunction, and autonomic disturbances including temperature, blood pressure, and nociception abnormalities. Some children have been noted with developmental and behavioral abnormalities. Tumors of neural crest origin have been identified in 25-33% of the patients. The etiology of ROHHAD syndrome and the cause of rapid onset obesity is unknown.
The aims of this study are to understand the whole transcriptome profiling of patient specific induced pluripotent cell (iPSC) derived hypothalamic neurons to understand the transcriptional level changes that give rise to the manifestations seen in ROHHAD syndrome.
Aim 1. Generate patient specific iPSC-derived hypothalamic neurons from children with ROHHAD syndrome and their unaffected first degree relatives.
Aim 2: Compare the whole transcriptome profiling of the patient derived cells compared to those of unaffected relatives and reference datasets to understand the differences in transcriptome that gives rise to ROHHAD syndrome.
Aim 3: Selected patients may be invited to participate for detailed metabolic phenotyping to understand the mechanisms of excessive weight gain.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cases of ROHHAD syndrome Children diagnosed with ROHHAD syndrome during the course of their clinical care by their physicians. The investigators will perform transcriptome profiling in this group. |
Diagnostic Test: Transcriptome profiling
The investigators will obtain blood to extract peripheral mononuclear cells. These cells will be used to generate patient specific hypothalamic cells that will be used for transcriptome profiling.
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| Control cohort Unaffected first degree family members. The investigators will perform transcriptome profiling in this group. |
Diagnostic Test: Transcriptome profiling
The investigators will obtain blood to extract peripheral mononuclear cells. These cells will be used to generate patient specific hypothalamic cells that will be used for transcriptome profiling.
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Outcome Measures
Primary Outcome Measures
- Changes in the transcriptome profile of hypothalamic cells of children with ROHHAD syndrome compared to their unaffected first degree relatives. [2 year]
The investigators will perform whole transcriptome profiling of iPSC-derived hypothalamic neurons and compare the whole genome sequencing to identify the changes that may give rise to the disease.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Children with ROHHAD syndrome
Exclusion Criteria:
- Children with known genetic causes of obesity
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston Children's Hospital | Boston | New York | United States | 02115 |
| 2 | Columbia University Irving Medical Center | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Columbia University
Investigators
- Principal Investigator: Vidhu Thaker, MD, Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AAAS4650
- P00018387