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Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): a collaborative review of the current understanding

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Abstract

Purpose

To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents.

Methods

The literature (1965–2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause.

Results

ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions.

Conclusion

ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype.

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Data availability

Data presented in this review was reported provided in respective publications that are available on PubMed.

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Authors and Affiliations

  1. Center for Autonomic Medicine in Pediatrics (CAMP), Division of Autonomic Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Ilya Khaytin, Susan M. Slattery, Casey M. Rand & Debra E. Weese-Mayer

  2. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Ilya Khaytin, Susan M. Slattery & Debra E. Weese-Mayer

  3. College of Graduate Health Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA

    A. Kaitlyn Victor

  4. Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada

    Sarah F. Barclay & Kyle C. Kurek

  5. Department of Neurology, Boston Children’s Hospital, Boston, MA, USA

    Leslie A. Benson

  6. Stanley Manne Children’s Research Center, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Ilya Khaytin, Susan M. Slattery, Casey M. Rand & Debra E. Weese-Mayer

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  1. Ilya Khaytin
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  2. A. Kaitlyn Victor
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  3. Sarah F. Barclay
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  4. Leslie A. Benson
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  5. Susan M. Slattery
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  6. Casey M. Rand
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  7. Kyle C. Kurek
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  8. Debra E. Weese-Mayer
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Contributions

Conceptualization: IK, SMS, KV, SB, LB, CMR, KCK, DEW-M. Literature search: IK, SMS, KV, SB, LB, CMR, KCK, DEW-M. Writing, original draft: IK, SMS, KV, SB, LB, CMR, KCK, DEW-M. Writing, review, editing: IK, SMS, KV, SB, LB, CMR, KCK, DEW-M. All authors read and approved the final manuscript.

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Correspondence to Ilya Khaytin.

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Khaytin, I., Victor, A.K., Barclay, S.F. et al. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): a collaborative review of the current understanding. Clin Auton Res 33, 251–268 (2023). https://doi.org/10.1007/s10286-023-00936-y

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