Anat Cell Biol.  2023 Dec;56(4):421-427. 10.5115/acb.23.056.

Analyzing the factors that contribute to the development of embryological classical type of bladder exstrophy

• Margiana R
• Juwita W
• Ima K
• Faizah Z
• Supardi S

• KMID: 2548893
• DOI: http://doi.org/10.5115/acb.23.056

Abstract

Bladder exstrophy is a rare congenital condition of the pelvis, bladder, and lower abdomen that opens the bladder against the abdominal wall, produces aberrant growth, short penis, upward curvature during erection, wide penis, and undescended testes. Exstrophy affects 1/30,000 newborns. The bladder opens against the abdominal wall in bladder exstrophy, a rare genitourinary condition. This study is vital to provide appropriate therapy choices as a basis to improve patient outcomes. This study may explain bladder exstrophy and provide treatment. Epispadias, secretory placenta, cloacal exstrophy, and other embryonic abnormalities comprise the exstrophy-spades complex. The mesenchymal layer does not migrate from the ectoderm and endoderm layers in the first trimester, affecting the cloacal membrane. Embryological problems define the exstrophy-aspidistra complex, which resembles epimedium, classic bladder, cloacal exstrophy, and other diseases. Urogenital ventral body wall anomalies expose the bladder mucosa, causing bladder exstrophy. Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure. External factors such as high maternal age, smoking moms, and high maternal body mass index have also been associated to bladder exstrophy. Valproic acid increases bladder exstrophy risk; chemicals and pollutants during pregnancy may increase bladder exstrophy risk. Bladder exstrophy has no identified cause despite these risk factors. Exstrophy reconstruction seals the bladder, improves bowel function, reconstructs the vaginal region, and restores urination.

Keyword

Congenital abnormalities; Bladder exstrophy; Fetal anomalies; Urogenital system; Reproductive health

Figure

• 

  Fig. 1 Course and variation of bladder exstrophy cases. CIC, clean intermittent catheterization.

• 

  Fig. 2 Supravesical fissure, a variant of extrophic bladder.

Reference

References

1. Bawa M, Samalad VM, Kanojia RP, Rao KL. 2011; Partial umbilical exstrophy with cecal patch and intact hindgut entering a cloaca: a new variant. J Pediatr Surg. 46:244–6. DOI: 10.1016/j.jpedsurg.2010.09.041. PMID: 21238678.

2. Beaudoin S, Simon L, Bargy F. 1997; Anatomical basis of a common embryological origin for epispadias and bladder or cloacal exstrophies. Surg Radiol Anat. 19:11–6. DOI: 10.1007/BF01627728. PMID: 9060111.

3. Sisca EM, Pakpahan C, Rezano A, Margiana R, Agustinus A, Tanojo TD. 2022; Adult patients with aphallia: were they fertile? Online J Biol Sci. 22:214–22. DOI: 10.3844/ojbsci.2022.214.222.

4. Liaw A, Cunha GR, Shen J, Cao M, Liu G, Sinclair A, Baskin L. 2018; Development of the human bladder and ureterovesical junction. Differentiation. 103:66–73. DOI: 10.1016/j.diff.2018.08.004. PMID: 30236462.

5. Reinfeldt Engberg G, Mantel Ä, Fossum M, Nordenskjöld A. 2016; Maternal and fetal risk factors for bladder exstrophy: a nationwide Swedish case-control study. J Pediatr Urol. 12:304.e1–7. DOI: 10.1016/j.jpurol.2016.05.035. PMID: 27499280.

6. Siffel C, Correa A, Amar E, Bakker MK, Bermejo-Sánchez E, Bianca S, Castilla EE, Clementi M, Cocchi G, Csáky-Szunyogh M, Feldkamp ML, Landau D, Leoncini E, Li Z, Lowry RB, Marengo LK, Mastroiacovo P, Morgan M, Mutchinick OM, Pierini A, Rissmann A, Ritvanen A, Scarano G, Szabova E, Olney RS. 2011; Bladder exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research, and an overview of the literature. Am J Med Genet C Semin Med Genet. 157C:321–32. DOI: 10.1002/ajmg.c.30316. PMID: 22002949. PMCID: PMC4512232.

7. Ebert AK, Reutter H, Ludwig M, Rösch WH. 2009; The exstrophy-epispadias complex. Orphanet J Rare Dis. 4:23. DOI: 10.1186/1750-1172-4-23. PMID: 19878548. PMCID: PMC2777855. PMID: 65614d386f3941d2b51877a3501196e5.

8. Maruf M, Benz K, Jayman J, Kasprenski M, Michaud J, Di Carlo HN, Gearhart JP. 2019; Variant presentations of the exstrophy-epispadias complex: a 40-year experience. Urology. 125:184–90. DOI: 10.1016/j.urology.2018.10.049. PMID: 30576745.

9. Baron ME. 2001; The encyclopaedia of medical imaging, vol. V. AJR Am J Roentgenol. 177:1346. DOI: 10.2214/ajr.177.6.1771346.

10. Inouye BM, Tourchi A, Massanyi EZ, Gearhart JP, Tekes A. 2014; Duplicated pelvic floor musculature and diastematomyelia in a cloacal exstrophy patient. J Radiol Case Rep. 8:8–14. DOI: 10.3941/jrcr.v8i10.2088. PMID: 25426220. PMCID: PMC4242151.

11. Kizilcan F, Tanyel FC, Hiçsönmez A, Büyükpamukçu N. 1994; Superior vesical fissure: an exstrophy variant or a distinct clinical entity. Eur Urol. 26:187–8. DOI: 10.1159/000475374. PMID: 7957478.

12. Kazmierski B, Whang G. 2020; Congenital bladder exstrophy with uterine didelphys and prolapse of both uterine horns: a case report. Clin Imaging. 67:55–7. DOI: 10.1016/j.clinimag.2020.05.022. PMID: 32516694.

13. Benz KS, Dunn E, Solaiyappan M, Maruf M, Kasprenski M, Jayman J, Michaud JE, Facciola J, DiCarlo H, Gearhart JP. 2018; Novel observations of female genital anatomy in classic bladder exstrophy using 3-dimensional magnetic resonance imaging reconstruction. J Urol. 200:882–9. DOI: 10.1016/j.juro.2018.04.071. PMID: 29723567.

14. Baradaran N, Cervellione RM, Orosco R, Trock BJ, Mathews RI, Gearhart JP. 2011; Effect of failed initial closure on bladder growth in children with bladder exstrophy. J Urol. 186:1450–4. DOI: 10.1016/j.juro.2011.05.067. PMID: 21855949.

15. Amalia TQ. 2018; Clinical aspects, diagnosis and management of nephrotic syndrome in children. 1:81–8. Indonesian. DOI: 10.1142/9789812384768_0005.

16. Becherucci F, Roperto RM, Materassi M, Romagnani P. 2016; Chronic kidney disease in children. Clin Kidney J. 9:583–91. DOI: 10.1093/ckj/sfw047. PMID: 27478602. PMCID: PMC4957724.

17. Zhang R, Knapp M, Suzuki K, Kajioka D, Schmidt JM, Winkler J, Yilmaz Ö, Pleschka M, Cao J, Kockum CC, Barker G, Holmdahl G, Beaman G, Keene D, Woolf AS, Cervellione RM, Cheng W, Wilkins S, Gearhart JP, Sirchia F, Di Grazia M, Ebert AK, Rösch W, Ellinger J, Jenetzky E, Zwink N, Feitz WF, Marcelis C, Schumacher J, Martinón-Torres F, Hibberd ML, Khor CC, Heilmann-Heimbach S, Barth S, Boyadjiev SA, Brusco A, Ludwig M, Newman W, Nordenskjöld A, Yamada G, Odermatt B, Reutter H. 2017; ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development. Sci Rep. 7:42170. DOI: 10.1038/srep42170. PMID: 28176844. PMCID: PMC5296905.

18. Sharma A, Dakal TC, Ludwig M, Fröhlich H, Mathur R, Reutter H. 2018; Towards a central role of ISL1 in the bladder exstrophy-epispadias complex (BEEC): computational characterization of genetic variants and structural modelling. Genes (Basel). 9:609. DOI: 10.3390/genes9120609. PMID: 30563179. PMCID: PMC6315746. PMID: d847724db2d24f37b4712f56712629fe.