Ondine curse and neurocristopathy

Area of Science:

• Pediatric Neurology
• Developmental Biology
• Genetics

Background:

• Congenital central hypoventilation syndrome (CCHS), or Ondine curse, is a rare disorder affecting autonomic respiratory control.
• Hirschsprung disease involves the congenital absence of ganglion cells in the distal bowel, leading to functional obstruction.
• The co-occurrence of these two conditions is exceptionally rare, prompting investigation into shared developmental pathways.

Observation:

• Two newborns, one male and one female, presented with both CCHS and Hirschsprung disease.
• Both infants exhibited hypoventilation during sleep and normal respiration while awake.
• Neurological abnormalities were noted, particularly in the more severely affected female infant.

Findings:

• The male infant experienced seizures and died at 18 months; his brain neuropathology was unremarkable.
• The female infant displayed severe neurological deficits, including unreactive pupils and deafness, indicative of neural crest developmental failure, and died at 40 days.
• While the precise etiology remains unknown, the association suggests a link between CCHS, Hirschsprung disease, and neural crest maldevelopment.

Implications:

• The findings suggest that disruptions in neural crest development may underlie the co-occurrence of CCHS and Hirschsprung disease.
• This association implicates the peripheral nervous system in the pathophysiology of CCHS.
• Further research is warranted to elucidate the shared genetic and developmental mechanisms connecting these complex congenital disorders.