The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis. To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. This publication highlights the potential overlap between ROHHAD syndrome and Smith-Magenis syndrome (SMS) and also presents retinoic acid-induced 1 (RAI1) as a candidate gene for children with morbid obesity.
- Thaker VV, Esteves KM, Towne MC, Brownstein CA, James PM, Crowley L, Hirschhorn JN, Elsea SH, Beggs AH, Picker J, Agrawal PB. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab. 2015 May;100(5):1723-30. PMID: 25781356; PMCID: PMC4422892.
Read More: The Journal of Clinical Endocrinology & Metabolism
- Research Center: Harvard Medical School
- Center Contribution: Dr. Vidhu Thaker and her colleagues, with the support of a Pilot and Feasibility Award from the Harvard NORC, identified a novel de novo mutation in RAI1, a known causative gene in Smith-Magenis Syndrome (SMS), in a child with morbid obesity and a clinical diagnosis of Rapid-onset Obesity, Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome.