Congenital central hypoventilation syndrome with Hirschsprung's disease due to PHOX2B gene mutation in a Turkish infant

The association of congenital central hypoventilation syndrome (also known as Ondine's curse) and Hirschsprung's disease is termed Haddad syndrome, which is an extremely rare disorder. Recent studies have described that the PHOX2B gene mutation was responsible for congenital central hypoventilation syndrome. We report a term newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnia and bowel obstructions. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease. PHOXB direct sequencing showed a heterozygous in-frame duplication of 21 bp leading to an expansion of +7 alanines within the 20 alanine stretch of the PHOX2B gene and confirmed our diagnosis. In addition to a high index of clinical suspicion, testing for PHOX2B mutation can assist in the diagnosis of congenital central hypoventilation syndrome and in the prediction of disease progression. Infants presenting with congenital central hypoventilation syndrome should also be screened for Hirschsprung's disease.