What is Rohhad syndrome?

ROHHAD Syndrome: A Rare and Life-Threatening Disorder

ROHHAD syndrome (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation) is a rare and potentially fatal disorder characterized by sudden obesity onset in early childhood, followed by hypothalamic dysfunction, breathing abnormalities, and autonomic nervous system dysregulation that requires aggressive respiratory monitoring and multidisciplinary management to prevent cardiorespiratory arrest. 1

Clinical Presentation and Diagnostic Features

ROHHAD syndrome typically presents with the following sequence of symptoms:

• Rapid-onset obesity: Children develop dramatic weight gain (20-40 pounds over 4-6 months) between ages 1.5-7 years 1
• Hypothalamic dysfunction: Manifests as:
  • Water imbalance disorders
  • Elevated prolactin levels
  • Altered puberty onset
  • Central hypothyroidism
  • Growth hormone deficiency
  • Adrenocortical insufficiency 2
• Hypoventilation: Often recognized after a respiratory infection, presenting as:
  • Obstructive sleep apnea
  • Central hypoventilation requiring ventilatory support 1
• Autonomic dysregulation: Including:
  • Low body temperature
  • Cold hands and feet
  • Severe bradycardia
  • Decreased pain perception 1

Additional features include:

• Neural crest tumors (ganglioneuromas or ganglioneuroblastomas) in up to 40% of cases 1, 3
• Behavioral disorders
• Strabismus and abnormal pupillary responses 1

Diagnostic Approach

Diagnosis is challenging as there is no specific genetic or laboratory test for ROHHAD. The diagnosis is based on:

1. Clinical presentation with the characteristic sequence of symptoms
2. Exclusion of other disorders, particularly Congenital Central Hypoventilation Syndrome (CCHS) through PHOX2B genetic testing 1

Mortality and Morbidity Considerations

ROHHAD syndrome carries significant mortality risk:

• Nearly half of children may experience cardiorespiratory arrest following viral infections 1
• Overall mortality rate is estimated between 50-60% 2
• Early recognition and intervention are critical to prevent sudden death 4

Management Approach

Management is supportive and requires a multidisciplinary team:

1. Respiratory management:

   • Regular monitoring for hypoventilation
   • Non-invasive ventilation for mild cases
   • Tracheostomy with mechanical ventilation for severe cases 1, 3

2. Endocrine management:

   • Hormone replacement therapies for specific deficiencies
   • Monitoring of water and electrolyte balance 5

3. Tumor surveillance:

   • Regular imaging to detect neural crest tumors 4

4. Experimental treatments:

   • Some case reports suggest potential benefit from immunomodulatory therapies (intravenous immunoglobulins, cyclophosphamide, rituximab) based on the autoimmune hypothesis, though results are variable 3

Distinguishing Features from Similar Conditions

It is crucial to differentiate ROHHAD from:

1. Common obesity: ROHHAD has distinctive hypothalamic, respiratory, and autonomic features
2. Genetic obesity syndromes: These typically lack the respiratory and autonomic components
3. CCHS (Congenital Central Hypoventilation Syndrome): CCHS is associated with PHOX2B mutations and typically presents in the neonatal period 1
4. Obesity Hypoventilation Syndrome (OHS): OHS typically occurs in adults with longstanding obesity rather than children with rapid-onset obesity 1

Key Pitfalls to Avoid

1. Delayed diagnosis: The rarity of the condition often leads to delayed recognition
2. Failure to monitor respiratory function: Hypoventilation can be insidious and lead to sudden death
3. Missing associated neural crest tumors: Thorough imaging is essential as tumors occur in up to 40% of cases
4. Inadequate multidisciplinary care: These patients require coordinated care from pulmonology, endocrinology, cardiology, and neurology 6

Early recognition of ROHHAD syndrome is critical to implement appropriate respiratory support and prevent life-threatening cardiorespiratory arrest. The condition should be considered in all children with rapid-onset obesity who develop any hypothalamic, respiratory, or autonomic abnormalities.