ROHHAD and Prader-Willi syndrome (PWS): Clinical and genetic comparison

Sarah F. Barclay*, Casey M. Rand, Lisa Nguyen, Richard J.A. Wilson, Rachel Wevrick, William T. Gibson, N. Torben Bech-Hansen, Debra E. Weese-Mayer

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a very rare and potentially fatal pediatric disorder, the cause of which is presently unknown. ROHHAD is often compared to Prader-Willi syndrome (PWS) because both share childhood obesity as one of their most prominent and recognizable signs, and because other symptoms such as hypoventilation and autonomic dysfunction are seen in both. These phenotypic similarities suggest they might be etiologically related conditions. We performed an in-depth clinical comparison of the phenotypes of ROHHAD and PWS and used NGS and Sanger sequencing to analyze the coding regions of genes in the PWS region among seven ROHHAD probands. Results: Detailed clinical comparison of ROHHAD and PWS patients revealed many important differences between the phenotypes. In particular, we highlight the fact that the areas of apparent overlap (childhood-onset obesity, hypoventilation, autonomic dysfunction) actually differ in fundamental ways, including different forms and severity of hypoventilation, different rates of obesity onset, and different manifestations of autonomic dysfunction. We did not detect any disease-causing mutations within PWS candidate genes in ROHHAD probands. Conclusions: ROHHAD and PWS are clinically distinct conditions, and do not share a genetic etiology. Our detailed clinical comparison and genetic analyses should assist physicians in timely distinction between the two disorders in obese children. Of particular importance, ROHHAD patients will have had a normal and healthy first year of life; something that is never seen in infants with PWS.

Original languageEnglish (US)
Article number124
JournalOrphanet journal of rare diseases
Volume13
Issue number1
DOIs
StatePublished - Jul 20 2018

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Keywords

  • Autonomic dysfunction
  • Genetics
  • Hypothalamus
  • Hypoventilation
  • Pediatric obesity
  • Prader Willi syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Barclay, S. F., Rand, C. M., Nguyen, L., Wilson, R. J. A., Wevrick, R., Gibson, W. T., Bech-Hansen, N. T., & Weese-Mayer, D. E. (2018). ROHHAD and Prader-Willi syndrome (PWS): Clinical and genetic comparison. Orphanet journal of rare diseases, 13(1), [124]. https://doi.org/10.1186/s13023-018-0860-0