[MIM 209 880]

(Ondine-Hirschsprung syndrome)

Very rare. Neurocristopathy associating Hirschsprung’s disease (see this term) to a congenital central alveolar hypoventilation (Ondine disease: see this topic). Ondine disease is due to a mutation (de novo or autosomal dominant transmission with incomplete penetrance (10 % of cases) of the PHOX2B gene (4p12). 90 % of cases have a polyalanine repeated expansion (PARM) adding 4 to 13 alanine to the 20-residue polyalanines. Congenital central alveolar hypoventilation is probably due to a central dysfunction of the integration of the afferent information received by chemoreceptors: there is an absence of ventilatory response to CO2, with a normal ventilation at in the awake state but a decrease in tidal volume and a variable decrease in respiratory rate (or even apnea) during sleep and more specifically in non-REM sleep. The incidence of Ondine disease is estimated at about 1/200,000 births and 15-20 % of these children have Hirschsprung’s disease, generally a form extending further than the splenic angle. Boys/girls ratio is 1:1 on contrary of isolated Hirschsprung's disease that is more frequent in boys. Conversely, 1.5 % of children with Hirschsprung disease have Ondine disease.

The association of the two diseases causes dysfunction of the autonomic nervous system: disorders of thermoregulation, heart rhythm and control of BP, dysmotility of the gut.

Increased risk of neuroblastoma and ganglioneuroma.

In case of chronic hypoxemia, there is a risk of chronic cor pulmonale.

Mortality is high (> 50 % in the French registry), mostly during the first 6 months of life.

Anesthetic implications:

Echocardiography to exclude pulmonary hypertension. Esophageal dysmotility. Ondine disease generally requires a tracheotomy or phrenic nerve pacing for night ventilation. As  far as possible, use short-acting general anesthetics and opiates, and each time it is feasible, use locoregional anesthesia techniques. A case of complete AVB associated with a bolus of 3 mg/kg propofol injection has been reported. Monitoring of temperature.

References : 

-        Sochala C, Van Deenen D, De Villé A, Govaerts MJM. 
Heart block following propofol in a child. 
Paediatr Anaesth 1999; 9: 349-51.

-         Lai D, Schroer B. 
Haddad syndrome: a case of an infant with central congenital hypoventilation syndrome and Hirschsprung disease. 
J Child Neurol 2008; 23: 341-3.

-         Prottengeier J, Munster T, Wintermeyer P, Schmidt J. 
Anaesthesia and orphan disease: Haddad syndrome (Ondine-Hirschsprung disease). 
Eur J Anaesthesiol 2014; 31: 339-340 

-        Broch A, Trang H, Montalva L, Berrebi D, Dauger S, Bonnard A.
Congenital central hypoventilation syndrome and Hirschsprung disease : a retrospective review of the French National Registry Center on 33 cases.
J Pediatr Surg 2019; 54: 235-30.

Updated: December 2019