Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome

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.

Inclusion Criteria:

- children with ROHHAD syndrome

Exclusion Criteria:

- children with known genetic causes of obesity