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

• Published in: Orphanet journal of rare diseases Vol. 13; no. 1; p. 124
• Main Authors: Barclay, Sarah F, Rand, Casey M, Nguyen, Lisa, Wilson, Richard J A, Wevrick, Rachel, Gibson, William T, Bech-Hansen, N Torben, Weese-Mayer, Debra E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-07-2018; BioMed Central; BMC
• Subjects: Autonomic dysfunction; Childhood obesity; Children & youth; Development and progression; Diagnosis; Genetic aspects; Genetics; Growth hormones; Hypothalamus; Hypotheses; Hypoventilation; Medical research; Mutation; Obesity; Obesity hypoventilation syndrome; Pediatric obesity; Pediatrics; Prader Willi syndrome; Rare diseases; Autonomic dysfunction; Genetics; Hypoventilation; Hypothalamus; Prader Willi syndrome; Pediatric obesity
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-018-0860-0

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.
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.
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.