Novel neuropathologic findings in the Haddad syndrome

Haddad syndrome (congenital central hypoventilation syndrome and Hirschsprung’s disease) is a rare disorder for which in-depth neuropathologic analysis is lacking. We report the brain findings in a full-term male infant with Haddad syndrome who died at 27 days of life. Bilateral hypoplasia of the superior temporal lobe and gyral anomalies in the frontal cortex were present. Immunohistochemistry with an antibody to tyrosine hydroxylase (noradrenaline synthesis) demonstrated hypoplasia of the locus coeruleus (implicated in chemoreception) and A5 region. Other findings included delayed maturation of the arcuate nucleus (putative human homologue of ventral medullary neurons in animals critical for chemoreception) and aberrant fascicles in the nucleus of the solitary tract. Efforts to determine the putative gene mutation were unsuccessful. This study implicates novel brain findings in Haddad syndrome mimicking those in murine Phox2b null mutants. This case suggests that abnormalities occur in CCHS in a network of sites critical to chemoreception.