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Endocrine Care: Pierre Bougnères, Letitia Pantalone, Agnès Linglart, Anya Rothenbühler, and Catherine Le Stunff Endocrine Manifestations of the Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neural Tumor Syndrome in Childhood J Clin Endocrinol Metab 2008; 93: 3971-3980 [Abstract] [Full text] [PDF]

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Facilitating the Diagnosis of ROHHAD Syndrome

Diego Ize-Ludlow, Debra E. Weese-Mayer. Professor of Pediatrics at Northwestern University Feinberg School of Medicine, Director, Center for Autonomic Medicine in Pediatrics (C.A.M.P.)   (19 September 2008)

Facilitating the Diagnosis of ROHHAD Syndrome 19 September 2008
Diego Ize-Ludlow, Assitant Professor of Clinical Pediatrics University of Illinois at Chicago, Department of Pediatrics, Division of Pediatric Endocrinology, Debra E. Weese-Mayer. Professor of Pediatrics at Northwestern University Feinberg School of Medicine, Director, Center for Autonomic Medicine in Pediatrics (C.A.M.P.) Send letter to journal: Re: Facilitating the Diagnosis of ROHHAD Syndrome diegoize{at}uic.edu Diego Ize-Ludlow, et al.	We have read with interest the report by Bougnčres et al (1) which supports our findings on the endocrine manifestations of the rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome (2). The authors suggest renaming the syndrome as “ROHHADNET” to warn physicians of the possibility of neural tumors including ganglioneuromas. In our opinion, because obesity, hypoventilation, and cardiac arrest typically present long before a child develops a neural crest tumor, the suggested modification of the acronym to include ”NET” for neural tumors in the ROHHAD acronym, essentially showcasing this aspect of the phenotype, could result in delayed awareness and diagnosis of ROHHAD. In our series reported in 2007, among the subset of subjects with neural crest tumors, the ganglioneuromas were identified up to 7 years after the initial manifestations of ROHHAD. In the report by Bougnčres et al., ganglioneuromas were identified up to 16 years after the initial manifestations. We believe that to facilitate early recognition of the complex ROHHAD phenotype, a life-threatening syndrome deserves an acronym that includes features reported in the majority of patients, thereby facilitating early and prompt identification. Failing to classify a patient as having ROHHAD due to absence of a neural crest tumor may be potentially fatal. There is significant clinical overlap between ROHHAD and other disorders of respiratory control with autonomic dysregulation. We know that PHOX2B mutation-confirmed Congenital Central Hypoventilation Syndrome (CCHS), a disorder that typically presents in the neonatal period, can also present later in childhood and adulthood (3). In order to distinguish ROHHAD from CCHS we demonstrated the absence of CCHS-related PHOX2B mutations in the ROHHAD subjects we described previously (2), and in a cohort that has grown to more than 30 cases followed in our program. Such genetic distinction was not applied to the Bougnčres et al (1) publication. It remains essential to perform PHOX2B Screening Testing, with sequel PHOX2B Sequencing testing in patients suspected of ROHHAD to clearly distinguish CCHS from ROHHAD (3). Only then can the similarities and differences of these related but distinct conditions reflecting respiratory and autonomic dysregulation be more clearly distinguished. We appreciate the authors’ recognition of referral bias in their report. Likewise readers of the Journal should be conscious of the lower frequency of neural tumors and growth deceleration (fewer than 50% and 30%, respectively) in our series (2). We continue to follow the reported patients and a growing dataset of children with ROHHAD, and note that the initially reported frequency of neural tumors may have been overestimated in our cohort. Consequently, we suspect that a higher frequency of ROHHAD will be identified without the addition to “NET” at the end of the ROHHAD acronym, and that a growing number of subjects will be identified before presenting with cardiopulmonary arrest and sequelae of alveolar hypoventilation. Our responsibility as physician-scientists caring for and studying these special children is to simplify and demystify complex disorders by improving early identification, with the long term goal of minimizing risk from physiologic compromise. Keeping the acronym simple, as ROHHAD, we are more likely to achieve that very goal. References 1. Bougnčres, P., Pantalone, L., Linglart, A., Rothenbuhler, A., and Le Stunff, C. 2008. Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation and neural tumor (ROHHADNET) syndrome in early childhood. J Clin Endocrinol Metab. jc.2008-0238v1 2. Ize-Ludlow D., Gray J., Sperling M.A., Berry-Kravis E.M., Milunsky J.M., Farooqi I.S., Rand C.M., and Weese-Mayer D.E. 2007. Rapid onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood. Pediatrics 120:e179-e188. 3. Weese-Mayer DE, Marazita EM, and Berry-Kravis EM. 2008. Congenital central hypoventilation syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource [database online], updated July, 2008. Copyright University of Washington, Seattle, 1997-2008. Available at http://www.genetests.org