Congenital central hypoventilation syndrome (CCHS) is a life-threatening disease that primarily manifests as sleep-associated respiratory insufficiency and a markedly impaired ventilatory response to hypercarbia and hypoxemia. Paired-like homeobox 2b (PHOX2B) gene mutations are known to cause CCHS. Almost all patients with CCHS are heterozygous for a poly-alanine expansion in PHOX2B. However, some patients have other germ-line abnormalities, including missense, nonsense and frame shift mutations. CCHS combined with Hirschsprung disease (Haddad syndrome) is extremely rare. Here, we report the case of a 1-day-old male neonate with recurrent apnea and bowel distension. Genetic analysis showed that he was heterozygous for a germ-line mutation in the PHOX2B gene. Only three cases of CCHS including two with Haddad syndrome confirmed by PHOX2B gene mutations have been reported in Korea. All of these cases have been heterozygous for a poly-alanine expansion mutation. This is the first report describing Haddad syndrome with a germ-line mutation in the PHOX2B gene in a Korean neonate.
Anoxia ; Apnea ; Frameshift Mutation ; Genes, Homeobox ; Germ-Line Mutation* ; Hirschsprung Disease ; Humans ; Hypoventilation ; Infant, Newborn* ; Korea ; Male ; Respiratory Insufficiency