Investigators at Ghent University Hospital, Belgium; Radboud University Nijmegen Medical Centre, and Sleep Medicine Centre, Heeze, Netherlands, report a 7-year-old girl with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD syndrome). In addition to dysfunction of endocrine, respiratory, and autonomic nervous systems, the patient developed daytime sleepiness, visual hallucinations, and episodic loss of facial muscle tone with slurred speech, suggestive of secondary narcolepsy and cataplexy. A nocturnal polysomnogram showing short sleep latency, sleep-onset REM period, and sleep fragmentation was compatible with narcolepsy, and absence of hypocretin-1 levels in the CSF was confirmatory. Noninvasive ventilation was attempted but was unsuccessful. Treatment was complicated by panic attacks and anxiety and by recurrent cardiac arrest in which she died. Ganglioneuroma or ganglioneuroblastoma was not detected. Autopsy was denied. [1]

COMMENT. Central hypoventilation syndrome is a rare heterogeneous disorder of early (congenital) or late, childhood onset of symptoms. Originally reported as Ondine’s curse, or primary alveolar hypoventilation syndrome, and presenting at birth [2], the association of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation is of late onset and has the acronym, ROHHAD [3]. The onset and timing of phenotypic features of the syndrome are variable, leading to delayed or missed diagnosis with potential fatality from hypoventilation and cardiorespiratory arrest.

Genetic testing of candidate genes in 15 children with ROHHAD syndrome. PHOX2B sequencing, the disease-causing gene in congenital central hypoventilation syndrome, revealed no mutations, demonstrating that late-onset ROHHAD is distinct from the congenital syndrome [4]. In addition to hyperphagia and obesity, respiratory alveolar hypoventilation, thermal and other autonomic dysregulation, patients with ROHHAD have hyperprolactinemia, diabetes insipidus, and tumors of neural crest origin. The report of narcolepsy as a manifestation of this mainly respiratory syndrome may lend support to the theory of an autoimmune-mediated process as a possible cause of ROHHAD. [5]