Os odontoideum in identical twins: Comparative gene expression analysis

BACKGROUND: Os odontoideum is a well identified anomaly of the craniovertebral junction. Since its initial description, there has been a continuous debate regarding the nature of its etiology: Whether congenital or traumatic. We sought to compare the gene expression profiles in patients with congenital os odontoideum, those with traumatic os odontoideum and controls. METHODS: We have evaluated a pair of identical twins both with os odontoideum. We identified two additional patients with and four subjects without os odontoideum. We analyzed the gene expression profiles in these patients using a custom TaqMan microarray and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The relative gene expression profiles in the two identical twins, the two nontwin patients with os odontoideum and the controls were assessed. RESULTS: A total of 213 genes with significantly different expression between the twin os odontoideum patients and the subjects without os odontoideum were detected. CACNG6, PHEX, CACNAD3, IL2, FAS, TUFT1, KIT, TGFBR2, and IGF2 were expressed at levels greater than 100-fold more in the twins. There were six genes with significantly different expression profiles in the twins as compared with the nontwin os odontoideum patients: CMK4, ATF1, PLCG1, TAB1, E2F3, and ATF4. There were no statistically significant differences in gene expression in the four patients with os odontoideum and the subjects without. Trends, however, were noted in MMP8, KIT, HIF1A, CREB3, PWHAZ, TGFBR1, NFKB2, FGFR1, IPO8, STAT1, COL1A1, and BMP3. CONCLUSIONS: Os odontoideum has multiple etiologies, both traumatic and congenital and perhaps some represent a combination of the two. This work has identified a number of genes that show increased expression in a pair of twins with congenital os odontoideum and also demonstrates trends in gene expression profiles between a larger group of os odontoideum patients and non-os patients. A number of these genes are related to bone morphogenesis and maintenance.