HLXB9 Homeobox Gene and Caudal Regression Syndrome

Background: Caudal regression syndrome (CRS) is a congenital heterogeneous constellation of caudal anomalies that include varying degrees of agenesis of the spinal column, anorectal malformations (ARMs), genitourinary anomalies, and pulmonary hypoplasia. The combination of a particular form of hemisacrum, ARM, and presacral mass (teratoma, anterior meningocele, rectal duplication, or a combination thereof) constitutes Currarino syndrome (CS). Previous reports have shown HLXB9 to be a major causative gene for CS. The aim of our study was to reevaluate the involvement of the HLXB9 gene in a larger group of CRS cases.

Methods: SSCP analysis was performed on a series of 48 CRS cases without CS. A case-control approach was used to test whether an alteration of the length of the GCC triplets in exon 1 of the HLXB9 gene could contribute to CRS risk.

Results: No pathological variants of the HLXB9 gene were identified by mutational analysis. We also found no evidence that the length of the GCC triplets had any effect on the CRS risk, even when the allelic frequencies were stratified according to the presence or absence of ARMs and the type of sacral agenesis.

Conclusions: We confirmed that the HLXB9 gene is not involved in the pathogenesis of CRS, and to date is known as a causative gene only for CS.