BEEC
MCID: BLD170
MIFTS: 43

Bladder Exstrophy and Epispadias Complex (BEEC)

Categories: Fetal diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Bladder Exstrophy and Epispadias Complex

MalaCards integrated aliases for Bladder Exstrophy and Epispadias Complex:

Name: Bladder Exstrophy and Epispadias Complex 57 6
Classic Exstrophy of the Bladder 58
Bladder Exstrophy 58
Beec 57

Characteristics:

Orphanet epidemiological data:

58
bladder exstrophy
Inheritance: Multigenic/multifactorial; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
upper urinary tract usually normal


HPO:

31
bladder exstrophy and epispadias complex:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare renal diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 600057
MESH via Orphanet 45 D001746
ICD10 via Orphanet 33 Q64.1
UMLS via Orphanet 72 C0005689
Orphanet 58 ORPHA93930
MedGen 41 C0005689

Summaries for Bladder Exstrophy and Epispadias Complex

OMIM® : 57 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 (Gearhart and Jeffs, 1998). BEEC is one of the most severe urologic birth defects because of its profound impact on continence, sexual function, and morbidity due to the effect of chronic and recurrent infections on renal function. The term 'exstrophy,' derived from the Greek work ekstriphein, which literally means 'turn inside out,' was first used by Chaussier in 1780. Martinez-Frias et al. (2001) emphasized that exstrophy of the cloaca and exstrophy of the bladder are 2 different expressions of a primary developmental field defect. Cloacal exstrophy is a feature of the OEIS (omphalocele-exstrophy-imperforate anus-spinal defects) complex (258040). Exstrophy of the cloaca includes the persistence and exstrophy of a common cloaca that receives ureters, ileum, and a rudimentary hindgut and is associated with failure of fusion of the genital tubercles and pubic rami, incomplete development of the lumbosacral vertebrae with spinal dysraphism, imperforate anus, cryptorchidism and epispadias in males and anomalies of the mullerian duct derivatives in females, and a wide range of urinary tract anomalies. Omphalocele is common, and most patients have a single umbilical artery. Reutter et al. (2016) reviewed the epidemiology, potential mechanisms, and animal models for BEEC. They described BEEC as a spectrum of component malformations of variable severity, including epispadias as the mildest phenotype and classic bladder exstrophy as the most common, with cloacal exstrophy representing the most severe form. In approximately one-third of cases, urologic malformations are present, including ectopic kidney, renal agenesis, and/or hydronephrosis. Other malformations involving the gastrointestinal, skeletal, spinal, and genitourinary systems, including cryptorchidism and ambiguous genitalia, are reported frequently. The authors noted that cloacal exstrophy is considered by some to have a different embryologic origin from classic bladder exstrophy. (600057) (Updated 05-Mar-2021)

MalaCards based summary : Bladder Exstrophy and Epispadias Complex, also known as classic exstrophy of the bladder, is related to bladder exstrophy-epispadias-cloacal exstrophy complex and bladder exstrophy. An important gene associated with Bladder Exstrophy and Epispadias Complex is ISL1 (ISL LIM Homeobox 1), and among its related pathways/superpathways are MicroRNAs in cancer and Signaling pathways regulating pluripotency of stem cells. The drugs Anesthetics and Anesthetics, General have been mentioned in the context of this disorder. Affiliated tissues include kidney, prostate and bone, and related phenotypes are inguinal hernia and epispadias

Related Diseases for Bladder Exstrophy and Epispadias Complex

Diseases related to Bladder Exstrophy and Epispadias Complex via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 132)
# Related Disease Score Top Affiliating Genes
1 bladder exstrophy-epispadias-cloacal exstrophy complex 32.0 WNT3 ISL1
2 bladder exstrophy 29.7 WNT3 TP63 ISL1
3 cleft lip 29.6 WNT3 TP63
4 cleft palate, isolated 29.4 WNT3 TP63
5 diphallia 11.1
6 sacral defect with anterior meningocele 11.1
7 urinary tract infection 10.7
8 pelvic organ prolapse 10.6
9 acute cystitis 10.6
10 vesicoureteral reflux 1 10.5
11 pyelonephritis 10.5
12 hypospadias 10.5
13 inguinal hernia 10.4
14 omphalocele 10.4
15 abdominal wall defect 10.4
16 neural tube defects 10.4
17 adenocarcinoma 10.3
18 metabolic acidosis 10.3
19 pain agnosia 10.3
20 urethral stricture 10.3
21 sexual disorder 10.3
22 anus, imperforate 10.2
23 neurogenic bladder 10.2
24 ischemia 10.2
25 isolated epispadias 10.2
26 cat eye syndrome 10.1
27 myelomeningocele 10.1
28 urolithiasis 10.1
29 cystitis 10.1
30 squamous cell carcinoma 10.1
31 infertility 10.1
32 duplication of urethra 10.1
33 bladder cancer 10.1
34 nephrolithiasis, calcium oxalate 10.1
35 polykaryocytosis inducer 10.1
36 digeorge syndrome 10.1
37 renal hypodysplasia/aplasia 1 10.1
38 cryptorchidism, unilateral or bilateral 10.1
39 gastroschisis 10.1
40 scoliosis 10.1
41 osteomyelitis 10.1
42 chronic pyelonephritis 10.1
43 leech infestation 10.1
44 azoospermia 10.1
45 oligospermia 10.1
46 orchitis 10.1
47 endometriosis 10.1
48 ureteral obstruction 10.1
49 nephrolithiasis 10.1
50 adenoma 10.1

Graphical network of the top 20 diseases related to Bladder Exstrophy and Epispadias Complex:



Diseases related to Bladder Exstrophy and Epispadias Complex

Symptoms & Phenotypes for Bladder Exstrophy and Epispadias Complex

Human phenotypes related to Bladder Exstrophy and Epispadias Complex:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 inguinal hernia 58 31 Frequent (79-30%) HP:0000023
2 epispadias 58 31 Very frequent (99-80%) HP:0000039
3 bladder exstrophy 58 31 Very frequent (99-80%) HP:0002836
4 bowel incontinence 58 Occasional (29-5%)
5 umbilical hernia 58 Very frequent (99-80%)
6 horseshoe kidney 31 HP:0000085
7 vesicoureteral reflux 58 Very frequent (99-80%)
8 intestinal malrotation 58 Occasional (29-5%)
9 recurrent urinary tract infections 58 Frequent (79-30%)
10 abnormality of pelvic girdle bone morphology 31 HP:0002644
11 hypoplasia of penis 58 Very frequent (99-80%)
12 abnormality of the ureter 58 Frequent (79-30%)
13 anteriorly placed anus 31 HP:0001545
14 omphalocele 58 Occasional (29-5%)
15 hydroureter 31 HP:0000072
16 unilateral renal agenesis 31 HP:0000122
17 abnormality of the anus 58 Very frequent (99-80%)
18 abnormality of the clitoris 58 Very frequent (99-80%)
19 bifid clitoris 31 HP:0030911

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Genitourinary Internal Genitalia Male:
inguinal hernia

Genitourinary External Genitalia Male:
epispadias

Genitourinary External Genitalia Female:
bifid clitoris

Abdomen Gastrointestinal:
anteriorly displaced anus

Skeletal Pelvis:
pubic diastasis

Genitourinary Kidneys:
horseshoe kidney
unilateral renal agenesis

Genitourinary Bladder:
bladder exstrophy

Genitourinary Ureters:
megaureter

Abdomen External Features:
displaced umbilicus (inferiorly)

Muscle Soft Tissue:
rectus abdominis muscle separation
rectus fascia separation

Clinical features from OMIM®:

600057 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Bladder Exstrophy and Epispadias Complex:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.43 ISL1 TP63 WNT3
2 limbs/digits/tail MP:0005371 9.33 ISL1 TP63 WNT3
3 no phenotypic analysis MP:0003012 9.13 ISL1 TP63 WNT3
4 normal MP:0002873 8.8 ISL1 TP63 WNT3

Drugs & Therapeutics for Bladder Exstrophy and Epispadias Complex

Drugs for Bladder Exstrophy and Epispadias Complex (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anesthetics
2 Anesthetics, General

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Transurethral Autologous Myoblast Injection for Treatment of Urinary Incontinence in Children With Bladder Exstrophy Unknown status NCT02075216 Phase 1, Phase 2
2 Phase I Study of Endoscopically Injected Muscle Derived Cells in Participants With Exstrophy-epispadias Complex Related Urinary Incontinence Terminated NCT01011777 Phase 1 MDC
3 Evaluation of Long-term Renal Function in Patients After Surgical Repair of Classical Bladder Exstrophy Unknown status NCT02192801
4 Navigation of the Pelvic Floor in Bladder Exstrophy Using Pre-operative MRI Completed NCT01878500
5 Biomechanical Assessment of Level Gait in Patient's Status Post Bladder Exstrophy Completed NCT00863070
6 Long Term Assessment and Outcome of Adult Patients With Congenital Genitourinary Abnormalities. Recruiting NCT03061084
7 Outcome Of Classic Bladder Exstrophy Repair, Assiut University Experience Not yet recruiting NCT04580186
8 Concomitant Renal and Urinary Bladder Allograft Transplantation Not yet recruiting NCT04626167 Early Phase 1
9 Urothelium Tissue Engineering Using Bladder Mucosa From Transurethral Resection of Prostate Not yet recruiting NCT03698721
10 Male Bladder Exstrophy in Adulthood : What Sexuality and Fertility Prospects ? Withdrawn NCT02759705
11 The Effect of Amniotic Membranes on Complex Genitourinary Reconstruction Outcomes in Pediatric and Adult Populations Withdrawn NCT03685955

Search NIH Clinical Center for Bladder Exstrophy and Epispadias Complex

Genetic Tests for Bladder Exstrophy and Epispadias Complex

Anatomical Context for Bladder Exstrophy and Epispadias Complex

MalaCards organs/tissues related to Bladder Exstrophy and Epispadias Complex:

40
Kidney, Prostate, Bone, Endothelial, Appendix

Publications for Bladder Exstrophy and Epispadias Complex

Articles related to Bladder Exstrophy and Epispadias Complex:

(show top 50) (show all 95)
# Title Authors PMID Year
1
SLC20A1 Is Involved in Urinary Tract and Urorectal Development. 61 57
32850778 2020
2
Genetics of Bladder-Exstrophy-Epispadias Complex (BEEC): Systematic Elucidation of Mendelian and Multifactorial Phenotypes. 61 57
27013921 2016
3
Seven new cases of familial isolated bladder exstrophy and epispadias complex (BEEC) and review of the literature. 57 61
12833402 2003
4
Bladder exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research, and an overview of the literature. 57
22002949 2011
5
Concordance analyses of twins with bladder exstrophy-epispadias complex suggest genetic etiology. 57
17937426 2007
6
Bladder exstrophy and Epstein type congenital macrothrombocytopenia: evidence for a common cause? 57
16969870 2006
7
Classic bladder exstrophy in a nonhuman primate: a comparative analysis. 57
11834381 2002
8
Exstrophy of the cloaca and exstrophy of the bladder: two different expressions of a primary developmental field defect. 57
11251990 2001
9
Creation of a model of bladder exstrophy in the fetal lamb. 57
8683791 1996
10
Four cases of bladder exstrophy in two families. 57
8071977 1994
11
The inheritance of the exstrophy-epispadias complex. 57
6737583 1984
12
Impact of bilateral ureteral reimplantation at the time of complete primary repair of bladder exstrophy on reflux rates, renogram abnormalities and bladder capacity. 61
33583747 2021
13
Molecular interactions at the bovine embryo-endometrial epithelium interface. 61
33112768 2020
14
Bull seminal plasma stimulates in vitro production of TGF-β, IL-6 and IL-8 from bovine endometrial epithelial cells, depending on dose and bull fertility. 61
32717675 2020
15
Outcomes of inflatable penile prosthesis insertion using a neotunica allograft in neophalluses of patients on the bladder exstrophy-epispadias complex spectrum. 61
32798107 2020
16
Variants in ALX4 and their association with genitourinary defects. 61
32385972 2020
17
Fertility and sexuality issues in congenital lifelong urology patients: female aspects. 61
32989556 2020
18
Health-Related Quality of Life in Patients with the Bladder Exstrophy-Epispadias Complex and Relationship to Incontinence and Sexual Factors: A Review of the Recent Literature. 61
32564346 2020
19
Bladder Herniation as an Auto-Augmentation Technique in Bladder Exstrophy: Initial Experience in Patients with Small Bladder Plate. 61
32105656 2020
20
Progesterone inhibits inflammatory response in E.coli- or LPS-Stimulated bovine endometrial epithelial cells by NF-κB and MAPK pathways. 61
31821816 2020
21
Fertility and sexuality issues in congenital lifelong urology patients: male aspects. 61
32067073 2020
22
Different effects of cortisol on pro-inflammatory gene expressions in LPS-, heat-killed E.coli-, or live E.coli-stimulated bovine endometrial epithelial cells. 61
31918707 2020
23
Isolated bladder exstrophy in prenatal diagnosis. 61
31115647 2019
24
Health-related quality of life among children, adolescents, and adults with bladder exstrophy-epispadias complex: a systematic review of the literature and recommendations for future research. 61
30725391 2019
25
Classic bladder exstrophy and adenocarcinoma of the bladder: Methylome analysis provide no evidence for underlying disease-mechanisms of this association. 61
31296310 2019
26
Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene. 61
31044557 2019
27
22q11.2 duplications in a UK cohort with bladder exstrophy-epispadias complex. 61
30628148 2019
28
Differential gene expression in bovine endometrial epithelial cells after challenge with LPS; specific implications for genes involved in embryo maternal interactions. 61
31487323 2019
29
Split-appendix Technique for Simultaneous Use in the Mitrofanoff Principle and Posterior Urethral Substitution in a Bladder Exstrophy-Epispadias Complex Patient. 61
30686891 2019
30
Towards a Central Role of ISL1 in the Bladder Exstrophy⁻Epispadias Complex (BEEC): Computational Characterization of Genetic Variants and Structural Modelling. 61
30563179 2018
31
Early detection of deep wound infection in bladder exstrophy and hypospadias using a novel intervention. 61
30332360 2018
32
The Cologne pouch procedure for continent anal urinary diversion in children with bladder exstrophy-epispadias complex. 61
30031742 2018
33
Re: Qualitative Questionnaire on the Psychosocial Wellbeing of Mothers of Children with BEEC. 61
30412963 2018
34
Preoperative care of Polypoid exposed mucosal template in bladder exstrophy: the role of high-barrier plastic wraps in reducing inflammation and polyp size. 61
29368874 2018
35
Effect of bovine seminal plasma on bovine endometrial epithelial cells in culture. 61
29105849 2018
36
Evaluation of the ISL1 gene in the pathogenesis of bladder exstrophy in a Swedish cohort. 61
29619236 2018
37
Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a. 61
29126155 2018
38
Bovine herpes virus type 4 alters TNF-α and IL-8 profiles and impairs the survival of bovine endometrial epithelial cells. 61
28546031 2017
39
[The German research network CURE-Net : A benefit for patients with rare diseases]. 61
28534165 2017
40
Psychosexual development management of bladder exstrophy epispadias in complex patients. 61
28254239 2017
41
Low-dose Human Chorionic Gonadotropin Stimulation Test as a Prognostic Incontinent Indicator in Boys With Bladder Exstrophy-epispadias Complex. 61
28039050 2017
42
Epispadias and the associated embryopathies: genetic and developmental basis. 61
27649475 2017
43
Dose related effects of LPS on endometrial epithelial cell populations from dioestrus cows. 61
27939589 2017
44
Qualitative questionnaire on the psychosocial wellbeing of mothers of children with BEEC. 61
27751835 2017
45
Comparing the bulking effect of calcium hydroxyapatite and Deflux injection into the bladder neck for improvement of urinary incontinence in bladder exstrophy-epispadias complex. 61
27896576 2017
46
Quality of life in female patients with bladder exstrophy-epispadias complex: Long-term follow-up. 61
27290615 2016
47
PLAGL1 epimutation and bladder exstrophy: Coincidence or concurrent etiology? 61
27223093 2016
48
Is 1p36 deletion associated with anterior body wall defects? 61
27144803 2016
49
CNV analysis in 169 patients with bladder exstrophy-epispadias complex. 61
27138190 2016
50
Bladder exstrophy-epispadias complex and the role of methylenetetrahydrofolate reductase C677T polymorphism: A case control study. 61
26862292 2016

Variations for Bladder Exstrophy and Epispadias Complex

ClinVar genetic disease variations for Bladder Exstrophy and Epispadias Complex:

6 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WNT3 NM_030753.5(WNT3):c.271T>C (p.Cys91Arg) SNV Likely pathogenic 189347 rs786205887 17:44851085-44851085 17:46773719-46773719
2 WNT7A NM_004625.4(WNT7A):c.487G>A (p.Ala163Thr) SNV Uncertain significance 189350 rs772935313 3:13896112-13896112 3:13854615-13854615
3 WNT11 NM_004626.3(WNT11):c.947G>A (p.Arg316His) SNV Uncertain significance 189352 rs758816226 11:75898227-75898227 11:76187183-76187183
4 FZD5 NM_003468.4(FZD5):c.267G>A (p.Met89Ile) SNV Uncertain significance 189354 rs756316536 2:208633197-208633197 2:207768473-207768473
5 LRP10 NM_014045.5(LRP10):c.754G>A (p.Gly252Ser) SNV Uncertain significance 189356 rs568022752 14:23344911-23344911 14:22875702-22875702
6 WNT3 NM_030753.5(WNT3):c.638G>A (p.Gly213Asp) SNV Uncertain significance 189357 rs786205889 17:44846116-44846116 17:46768750-46768750
7 LZTR1 NM_006767.4(LZTR1):c.2093C>T (p.Ser698Phe) SNV Uncertain significance 548121 rs760064852 22:21350275-21350275 22:20995986-20995986
8 LZTR1 NM_006767.4(LZTR1):c.1146G>A (p.Ser382=) SNV Uncertain significance 548122 rs751444145 22:21346655-21346655 22:20992366-20992366
9 ISL1 NM_002202.3(ISL1):c.479-4G>A SNV Uncertain significance 373894 rs2303750 5:50685476-50685476 5:51389642-51389642
10 ISL1 NM_002202.3(ISL1):c.137C>G (p.Ala46Gly) SNV Uncertain significance 374407 rs755382547 5:50680483-50680483 5:51384649-51384649
11 WNT10A NM_025216.3(WNT10A):c.487C>T (p.Arg163Trp) SNV Uncertain significance 189351 rs368280129 2:219754816-219754816 2:218890094-218890094
12 WNT6 NM_006522.4(WNT6):c.570G>A (p.Arg190=) SNV Likely benign 189349 rs786205888 2:219736475-219736475 2:218871753-218871753

Expression for Bladder Exstrophy and Epispadias Complex

Search GEO for disease gene expression data for Bladder Exstrophy and Epispadias Complex.

Pathways for Bladder Exstrophy and Epispadias Complex

Pathways related to Bladder Exstrophy and Epispadias Complex according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.65 WNT3 TP63
2 11.11 WNT3 ISL1
3 10.75 TP63 ISL1

GO Terms for Bladder Exstrophy and Epispadias Complex

Biological processes related to Bladder Exstrophy and Epispadias Complex according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.5 WNT3 TP63 ISL1
2 neuron differentiation GO:0030182 9.37 WNT3 ISL1
3 embryonic forelimb morphogenesis GO:0035115 9.26 WNT3 TP63
4 embryonic hindlimb morphogenesis GO:0035116 9.16 WNT3 TP63
5 anatomical structure formation involved in morphogenesis GO:0048646 8.96 WNT3 TP63
6 negative regulation of intracellular estrogen receptor signaling pathway GO:0033147 8.62 TP63 ISL1

Molecular functions related to Bladder Exstrophy and Epispadias Complex according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein domain specific binding GO:0019904 8.62 WNT3 TP63

Sources for Bladder Exstrophy and Epispadias Complex

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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