Rapid-onset
obesity with hypothalamic dysfunction,
hypoventilation, and autonomic dysregulation (ROHHAD) falls within a group of pediatric disorders with both respiratory control and autonomic nervous system dysregulation. Children with ROHHAD typically present after 1.5 years of age with rapid
weight gain as the initial sign. Subsequently, they develop alveolar
hypoventilation, autonomic nervous system dysregulation, and, if untreated, cardiorespiratory arrest. To our knowledge, this is the first report of discordant presentation of ROHHAD in monozygotic twins. Twin girls, born at term, had concordant growth and development until 8 years of age. From 8 to 12 years of age, the affected twin developed features characteristic of ROHHAD including
obesity, alveolar
hypoventilation,
scoliosis, hypothalamic dysfunction (
central diabetes insipidus,
hypothyroidism, premature pubarche, and
growth hormone deficiency), right paraspinal/thoracic
ganglioneuroblastoma,
seizures, and autonomic dysregulation including altered pain perception, large and sluggishly reactive pupils,
hypothermia, and profound
bradycardia that required a cardiac pacemaker. Results of genetic testing for PHOX2B (
congenital central hypoventilation syndrome disease-defining gene) mutations were negative. With early recognition and
conservative management, the affected twin had excellent neurocognitive outcome that matched that of the unaffected twin. The unaffected twin demonstrated rapid
weight gain later in age but not development of signs/symptoms consistent with ROHHAD. This discordant twin pair demonstrates key features of ROHHAD including the importance of early recognition (especially
hypoventilation), complexity of signs/symptoms and
clinical course, and importance of initiating comprehensive, multispecialty care. These cases confound the hypothesis of a monogenic etiology for ROHHAD and indicate alternative etiologies including autoimmune or epigenetic phenomenon or a combination of
genetic predisposition and acquired precipitant.