Epidemiological Survey of 214 Families With Bladder Exstrophy-Epispadias Complex

Abstract

Purpose-To identify causative non-genetic and genetic risk factors to the bladder exstrophyepispadias complex (BEEC).Materials and Methods-237 BEEC families were invited to participate and information was obtained from 214 families, mainly comprising European countries.Results-Two families showed familial occurrence. Male predominance (p 0.001) was found among all BEEC subgroups comprising epispadias (E), classical exstrophy of the bladder (CBE) or cloacal exstrophy (CE), with male to female ratios of 1.4, 2.8, and 2.0, respectively. No association with parental age, maternal reproductive history or with periconceptional maternal exposure to alcohol, drugs, chemical noxa, radiation or infections was found. However, periconceptional maternal exposure to smoking (p 0.009) was significantly more common for CE patients than for the combined group of E/CBE patients. Only 16.8% of mothers followed the current recommendations *Correspondence to: Michael Ludwig, Ph.D., Dept. of Clinical Biochemistry and Clinical Pharmacology, University of Bonn, SigmundFreud-Str. 25, D-53105 Bonn, Germany. E-mail: E-mail: mludwig@uni-bonn.de. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of periconceptional folic acid supplementation. 17.6% had started supplementation before the 10 th week of gestation. Interestingly, in the latter group, mothers of CE patients were more compliant (p 0.037) than mothers of the combined group of E/CBE patients. Furthermore, mothers of CE children knew significantly more often prenatally that their child would have a congenital malformation (p < 0.0001) than mothers of E/CBE children.Conclusions-Our study corroborates the hypothesis that E, CBE and CE are causally related, representing a spectrum of the same developmental defect, with a small risk of recurrence within families. Embryonic exposure to maternal smoking appears to enforce the severity, whereas periconceptional folic acid supplementation does not seem to alleviate it. There is a disproportional prenatal ultrasound detection rate between severe and mild phenotypes, possibly due to the neglect of imaging of full urinary bladders with focus on neural tube defects.

Evidence for linkage of the bladder exstrophy‐epispadias complex on chromosome 4q31.21‐22 and 19q13.31‐41 from a consanguineous iranian family

“…The combined prevalence of the BEEC spectrum among newborns of European descent is approximately 1 in 10,000, with an overall male-to-female ratio of approximately 2:1 (Ludwig et al, 2009b). Although BEEC can occur as part of a complex malformation syndrome, the majority (approximately 98.5%) of cases are classified as nonsyndromic (Ives et al, 1980;Shapiro et al, 1984;Boyadjiev et al, 2004;Gambhir et al, 2008).…”

Male Genitourinary System

“…However, there was an association of periconceptional maternal exposure to smoking in patients with cloacal exstrophy compared to patients with epispadias/ classic bladder exstrophy (Gambhir et al 2008). …”

p63 (TP73L) a key player in embryonic urogential development with significant dysregulation in human bladder exstrophy tissue

“…History of pregnancy was uneventful in all cases, without any maternal exposure to environmental toxins or maternal infections (15,18).…”