Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndromeand anorectal malformations with sacral hypodevelopment

Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sa cral hypodevelopment while the hemisacrum is characteristic of the Currarin o syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region? sonic hedgehog (SHH) wa s thought to represent a candidate gene for CS as well as for ARM with diff erent levels of sacral hypodevelopment according to its role in the differe ntiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large family with recurrence of CS. In addition, the screeni ng of SHH in 7 CS and in 15 sporadic ARM patients with sacral hypodevelopme nt allowed us to exclude its role in the pathogenesis of these disorders.