Smith-Lemli-Opitz syndrome (SLOS) is a syndrome of rare multiple congenital anomalies/mental retardation associated with low plasma cholesterol levels. Prior to receiving the diagnosis of SLOS, affected children may present as a neonatal surgical emergency with ambiguous genitalia, Hirschsprung's disease, and pyloric stenosis. We present two fatal cases of SLOS with near-total Hirschsprung's disease; the surgical, anaesthetic, and medical aspects of the cases are discussed, and a literature review is presented.