Monozygotic twins discordant for ROHHAD phenotype

Area of Science:

• Pediatric Endocrinology
• Neuroscience
• Genetics

Background:

• Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a complex pediatric disorder.
• It involves respiratory control and autonomic nervous system dysregulation, typically presenting after 1.5 years with rapid weight gain.
• Untreated ROHHAD can lead to cardiorespiratory arrest.

Observation:

• This study reports the first case of discordant ROHHAD in monozygotic twins.
• One twin developed classic ROHHAD features from age 8-12, including obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysregulation.
• The unaffected twin showed later weight gain but no ROHHAD symptoms; genetic testing for PHOX2B mutations was negative.

Findings:

• The discordant presentation challenges a purely monogenic etiology for ROHHAD.
• Early recognition of hypoventilation and comprehensive multispecialty care are crucial for favorable neurocognitive outcomes.
• Alternative etiologies like autoimmune or epigenetic factors are suggested.

Implications:

• This case underscores the complexity and variable presentation of ROHHAD.
• It emphasizes the need for early diagnosis and intervention, particularly for hypoventilation.
• The findings prompt further research into non-genetic factors contributing to ROHHAD development.