Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) Syndrome Presented by Hari Krishnan Nair

1. Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) Syndrome
Hari Krishnan Nair,
Visiting Medical Student,
Department of Neurology,
Boston Children’s Hospital.

2. A disorder of autonomic nervous system regulation with endocrine abnormalities.

3. Epidemiology and Etiopathogenesis

4. Epidemiology
A rare condition
Approximately 100 cases reported in the literature and clinically to date
Predominantly in patients of Caucasian and Arabic descent
◦One case each of Japanese, Indian and Malaysian origin

5. Etiology and Pathogenesis
No specific cause has been found to date
PHOX2B mutations, which causes a related disorder Congenital Central Hypoventilation Syndrome, are absent in ROHHAD

6. Clinical Presentation

7. Clinical Presentation
Children are apparently healthy until 1.5 years of age
Subsequently rapid-onset weight gain (often 30 pounds in 6-12 months)
◦Invariably the first symptom to appear
Hyperphagia
Hypersomnolence

8. Respiratory manifestations (Median age: 6.2 years)
Alveolar hypoventilation
◦Very shallow breathing during sleep
Cardiorespiratory arrest
Obstructive sleep apnea

9. Autonomic dysregulation (Median age: 3.6 years)
Altered pupillary response to light
Strabismus
Altered GI motility
◦Chronic constipation or diarrhea
Thermal dysregulation
◦Hyperthermia or hypothermia
Altered pain perception

10. Autonomic dysregulation
Bradycardia
Altered sweating
Adipsic Hypernatremia
Hyperprolactinemia
Diabetes insipidus

11. Cardiac abnormalities
Arrhythmias
Blood pressure dysregulation
Right ventricular hypertrophy secondary to cor pulmonale

12. Anatomic malformations of ANS
33-39%
Tumors of neural crest origin
◦Ganglioneuromas
◦Ganglioneuroblastomas
As late as 7-16 years after the onset of obesity

13. Neurobehavioral disorders
Behavioral, mood, and developmental disorders
Seizures – may be related to episodes of hypoxemia due to inadequate ventilator support
Ataxia

14. Diagnostic Modalities

15. Clinical Testing
Overnight polysomnography
◦For signs of obstructive sleep apnea and central hypoventilation
Imaging of chest and abdomen
◦To screen for evidence of neural crest tumors
Cardiac evaluation
Endocrine evaluation
◦Water balance regulation
◦Pituitary function

16. Sequential comprehensive evaluation
Annual physiologic assessment during spontaneous breathing awake and during sleep
72-hour Holter recording annually to evaluate for bradycardia
Echocardiogram annually
Neurocognitive testing annually

17. Management

18. Treatment
No specific treatment
Based on the clinical features and their relative severity
Multidisciplinary care at a tertiary center

19. Obesity
Emphasis to avoid further weight gain
◦In consultation with a nutritionist and endocrinologist
◦Recommend only modest exertion, with end tidal carbon dioxide and pulse oximetry
(as patients do not increase their breathing adequately during physical exertion)

20. Hypothalamic dysfunction
Hormone replacement
◦Growth hormone administration, and dopamine agonists to normalize prolactin levels have not been shown to modify the clinical course
Strict fluid intake regimen

21. Breathing deficit
Artificial ventilation
◦Intially – during sleep only
◦Later – continuous support
Most children – Mask ventilation and BiPAP at night
Some – 24-hour mechanical ventilation with tracheostomy

22. Autonomic dysregulation
Permanent pacemakers for bradycardia
Careful regulation of ambient temperature
Neural crest tumors – surgical removal
◦Has not interrupted the unfolding of the ROHHAD phenotype nor induced recovery from the ROHHAD phenotype

23. ROHHAD FIGHT Inc.
www.rohhadfight.org

24. Thank you