Haddad, syndrome
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(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