Bladder exstrophy‐epispadias complex

Abstract

The bladder exstrophy-epispadias complex (BEEC) represents an anterior midline defect with variable expression comprising a spectrum of anomalies involving the abdominal wall, pelvis, urinary tract, genitalia, and occasionally the spine and anus. The vast majority of BEEC cases are classified as non-syndromic and the etiology of this malformation is still unknown. This review presents the current state of knowledge on this multifactorial disorder, including historical retrospect, phenotypic and anatomical characterization, epidemiology, proposed developmental mechanisms, existing animal models, and implicated genetic and environmental components. These published lines of evidence argue strongly that BEEC occurs as a result of strong genetic predisposition that is yet to be deciphered.

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

“…Epispadias is the mildest form of this spectrum and exstrophy of the cloaca (EC), often referred to as the OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects), is the most severe form (Gearhart, 2002;Carey, 2001). 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).…”

“…To date, approximately 30 families with two or more affected individuals have been reported (Shapiro et al, 1984;Reutter et al, 2003;Ludwig et al, 2009b). In principle, the existence of these families allows the application of familybased linkage studies to identify the chromosomal location of disease-related genes.…”

Y chromosome aberration in a patient with cloacal-bladder exstrophy-epispadias complex: an unusual finding

“…Numerical chromosomal aberrations (47,XXX; 47,XXY; 47,XYY; 45,X/46,XX) were observed. In some of these cases Down syndrome was observed (9). Aneuploidy of sex chromosomes in some of these cases might point to loci involved in the formation of BEEC (1).…”

Genome-wide expression profiling of urinary bladder implicates desmosomal and cytoskeletal dysregulation in the bladder exstrophy-epispadias complex

“…To further validate the candidate genes, we analyzed their chromosomal localization for physical overlap with regions of putative linkage/linkage disequilibrium identified by our recent work and breakpoints of chromosome rearrangements observed in BEEC patients. Seven candidate genes, SLC8A1, FLNC, CALD1, SYNPO2, RRM2, ROD1, and ASS1, showed partial or complete physical overlap with regions of putative linkage or breakpoints of chromosome rearrangements in BEEC patients (7,26). All these genes were integrated in 5 of our top 10 biological networks: CALD1 in network 1, ASS1, SLC8A1 and SYNPO2 in network 2, RRM2 in network 3, FLNC in network 6, and ASS1 and ROD1 in network 9 (Table II).…”

“…Therefore, the expression pattern of candidate genes at these developmental stages can be taken as an indication of their functional relevance during early development of the bladder primordium and its associated tissues. To further validate candidate genes, we analyzed their chromosomal localization for physical overlap with regions of putative linkage/linkage disequilibrium identified by our recent work and breakpoints of chromosome rearrangements observed in BEEC patients (7,26,27).…”