Clinical and molecular characterization of the bladder exstrophy-epispadias complex: analysis of 232 families
Article first published online: 6 DEC 2004
Volume 94, Issue 9, pages 1337–1343, December 2004
How to Cite
Boyadjiev, S. A., Dodson, J. L., Radford, C. L., Ashrafi, G. H., Beaty, T. H., Mathews, R. I., Broman, K. W. and Gearhart, J. P. (2004), Clinical and molecular characterization of the bladder exstrophy-epispadias complex: analysis of 232 families. BJU International, 94: 1337–1343. doi: 10.1111/j.1464-410X.2004.05170.x
- Issue published online: 6 DEC 2004
- Article first published online: 6 DEC 2004
- Accepted for publication 22 July 2004
- bladder exstrophy;
Authors from John Hopkins University School of Medicine in Baltimore present their study into the identifying genetic and non-genetic factors contributing to the risk of bladder exstrophy-epispadias complex. They found it to occur most commonly as an isolated sporadic birth defect, and found no evidence of a single-gene effect or a common environmental factor.
To identify genetic and nongenetic factors contributing to the risk of bladder exstrophy-epispadias complex (BEEC).
PATIENTS AND METHODS
In all, 285 families with BEEC were invited to participate in the study, and 232 of them were recruited. Epidemiological information was obtained from 151 of the consenting families, with a detailed clinical genetic examination of 94 probands. In all, 440 DNA samples were collected from 163 families for molecular analysis.
Most of the cases were sporadic and had no family history of BEEC. Among patients, 95% were Caucasian, and males were more common in both the epispadias group (M/F, 2.2, 29 patients) and the classic bladder-exstrophy group (M/F 1.8, 164), but in the cloacal exstrophy group the sex ratio was close to unity (1.1, 15). There was a statistically significant association with advanced parental age (P < 0.001). Birth weight, gestational age and maternal reproductive history did not appear to be significantly different from those in the general population. Information on exposures to tobacco, alcohol and drugs was collected but none appeared to act as a risk factor. Karyotype analysis on 37 cases detected two chromosomal abnormalities, i.e. 46XY t(8;9)(p11.2; q13) and 47XYY. Molecular analysis of the HLXB9 gene, which causes Currarino syndrome, did not detect mutations in the blood or bladder DNA of 10 patients with bladder or cloacal exstrophy.
BEEC most commonly occurs as an isolated sporadic birth defect with a recurrence risk of << 1%. There was no evidence of a single-gene effect or common environmental factor in this study population. In addition to race and advanced parental age, birth order may be a risk factor for BEEC. We suggest somatic mutations in a gene(s) within the pathway regulating bladder development may be the cause of BEEC.