Genetic and molecular biological aspects of the bladder exstrophy-epispadias complex (BEEC)

Abstract

The bladder exstrophy and epispadias complex (BEEC) is an anterior midline defect with variable expression involving the infraumbilical abdominal wall including the pelvis, urinary tract, and external genitalia. The incidence varies with regard to ethnical background, sex, and phenotypic expression, and an incidence of 1:20,000 to 1:80,000 has been observed in the middle European population. No gene defect has been attributed to BEEC thus far and chromosomal aberrations or genetic syndromes associated with BEEC have only rarely been reported. According to epidemiological data, a complex genetic as well as a multifactorial mode of inheritance could underlie BEEC. However, no single teratogenic agent or environmental factor has been identified, which could play a dominant role in the expression of the BEEC.A risk of recurrence of 0.5-3% has been described in families with one affected subject. These values correspond to an increased recurrence risk estimated to be as high as 200- to 800-fold when compared to the common population. Due to the paucity of affected sib pairs and suitable multiplex families, conventional linkage analysis to identify candidate genes causally related with BEEC appears to be unfeasible. Large association studies and consecutive linkage disequilibrium mapping should therefore lead to the identification of candidate genes. Also new methods including matrix-based comparative genomic hybridization (CGH) are promising and have successfully been used in the past (e.g., CHARGE association). Moreover, the low incidence of the BEEC requires close cooperation between clinicians in the operative and nonoperative specialties as well as geneticists for successful gene search.

Pregnancy in case of exstrophy of bladder

“…3 There is 0.5-3 % risk of recurrence in families with one affected member. 4 It can occur as an isolated syndrome or may be associated with multiple congenital anomalies which include epispadias-exstrophy complex, anal defects, omphalocele, neural tube defects, and skeletal defects such as omphalocele, exstrophy of bladder, imperforate anus, spinal defects (OEIS) complex. 2 Pathogenesis of bladder exstrophy remains unknown.…”

Genetic Aspects of Congenital Urologic Anomalies

“…In the past, it was not possible to study this malformation other than with chromosome analysis by karyotyping. Several case reports in the literature on chromosomal aberrations indicate different chromosomal regions, without consistent findings [44]. In most cases, bladder exstrophy is an isolated, sporadic disorder; however, the reported concordance rate in twins indicates a genetic background because incidence of the condition is much higher in monozygotic than in dizygotic twins (45% and 6%, respectively) [45].…”

Family‐based association study of the MTHFR polymorphism C677T in the bladder‐exstrophy‐epispadias‐complex

“…In the present study, we investigated the MTHFR 677C → T polymorphism for association with the occurrence of the isolated non‐syndromic bladder‐exstrophy‐epispadias complex (BEEC), an anterior midline defect with variable expression involving the anterior abdominal wall, the pelvis, urinary tract, and external genitalia [Ludwig et al, 2005]. Exstrophy of the bladder (EB) represents the most common form in the BEEC spectrum, ranging from epispadias as the mildest to exstrophy of the cloaca (EC) as the most severe form [Carey, 2001].…”