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Biomolecules Jul 2023The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the...
BACKGROUND
The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well.
METHODS
Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2.
RESULTS
The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (, ), four candidate genes with autosomal-recessive biallelic variants (, , , ) and one candidate gene with suggestive uniparental disomy (). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in (c.978_985del, p.Ser327fster6) and in (c.1087delC, p.Arg363fster68).
CONCLUSIONS
According to previous studies, our study further implicates in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed.
Topics: Male; Humans; Bladder Exstrophy; Epispadias; Exome; Urinary Bladder; Calcium-Binding Proteins; Membrane Proteins; Transcription Factors
PubMed: 37509153
DOI: 10.3390/biom13071117 -
Urology Case Reports Nov 2023A one-day old full-term female neonate presented with a duplicate bladder and exstrophy variant including a patch of exstrophic or ectopic mucosa, duplicate vagina,...
A one-day old full-term female neonate presented with a duplicate bladder and exstrophy variant including a patch of exstrophic or ectopic mucosa, duplicate vagina, uterus, and two complete bladders. We report on the surgical management performed in this case and functional urinary results based on a synchronous urodynamic study of the duplicate bladders. To our knowledge, the occurrence of duplicate bladder exstrophy variant with complete urinary continence has not been previously reported.
PubMed: 38046258
DOI: 10.1016/j.eucr.2023.102610 -
Anatomy & Cell Biology Dec 2023Bladder exstrophy is a rare congenital condition of the pelvis, bladder, and lower abdomen that opens the bladder against the abdominal wall, produces aberrant growth,... (Review)
Review
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.
PubMed: 37649128
DOI: 10.5115/acb.23.056 -
Indian Journal of Pathology &... Nov 2023Bladder exstrophy is a rare congenital anomaly in which the urinary bladder develops outside the body. It may be part of the bladder epispadias-exstrophy-cloacal...
Bladder exstrophy is a rare congenital anomaly in which the urinary bladder develops outside the body. It may be part of the bladder epispadias-exstrophy-cloacal complex, which is a serious embryological defect where a spectrum of abnormalities involving the urinary tract, genital tract, musculoskeletal system, and intestinal tract is seen. Primary signet ring cell adenocarcinoma (PSRCA) arising in exstrophy of the urinary bladder is extremely rare with only a few cases reported in the literature. A 32-year-old man with congenital, untreated bladder exstrophy presented with a large fungating mass on the lower abdominal wall. Physical examination revealed a 15 × 12 cm exophytic mass with a penile epispadias. Ultrasonography showed a replacement of the urinary bladder by a mass of size 9 × 8 × 7 cm with a defect in the abdominal wall. On Contrast-enhanced computed tomography (CECT), a mass protruding from a large, inferior abdominal wall defect of 5.3 cm was seen. Widened pubic symphysis with divarication of recti and an absent urinary bladder, consistent with bladder exstrophy, was also noted. The biopsy showed a signet ring cell adenocarcinoma. A radical cystectomy with ileal conduit and left inguinal lymph node dissection was done. Histopathology examination revealed a PSRCA with metastasis to the left inguinal lymph nodes. Immunohistochemistry (IHC) showed strong positivity with CDX2 and CK20 while CK7 was negative. PSRCA shows an aggressive behavior, as was seen in our case, which had metastatic inguinal lymph nodes at the time of presentation. Metastatic signet ring cell adenocarcinomas from other sites need to be ruled out. Bladder exstrophy can develop high-grade malignancies at any stage of life. Hence, surgical treatment early in life with lifelong follow-up is recommended.
PubMed: 38394437
DOI: 10.4103/ijpm.ijpm_1025_22 -
African Journal of Paediatric Surgery :... 2023Classical bladder exstrophy is a congenital anomaly whose management and outcome has advanced over years. Management and outcome are better when management starts at the...
Classical bladder exstrophy is a congenital anomaly whose management and outcome has advanced over years. Management and outcome are better when management starts at the newborn period. This was the management of a neglected bladder exstrophy in a male presenting at 16 years of age. We report our challenges, management and outcome to highlight the rarity of this presentation, and the adaptation to the usual protocol of care. The patient presented at 16 years of age with classic bladder exstrophy. The bladder plate was contracted and had cystitis. The patient had a modification of complete primary repair of exstrophy (CPRE) with bilateral pelvic osteotomy stabilised with a 7-hole plate and 4 screws, then bladder neck reconstruction + bladder augmentation + cross-trigonal neocystoureterostomy in a 12-h procedure. He had surgical site infection, superficial wound breakdown and vesicocutaneous fistula that all healed with dressing and prolonged suprapubic cystostomy drainage. He achieved some degree of urinary continence and ability to void, though he still has stress incontinence and frequency at 6 months of follow-up. He has a micturition interval of 60-120 min, and is expected to improve. Presentation and repair of classic bladder exstrophy in the adolescent is very rare in the literature and therefore no known standard of care. This report adds to the body of knowledge. Again, this experience lends credence to the proponents of CPRE in reducing the number of procedures required to treat exstrophy.
Topics: Infant, Newborn; Humans; Male; Adolescent; Bladder Exstrophy; Urinary Incontinence; Urologic Surgical Procedures; Urination; Plastic Surgery Procedures; Treatment Outcome; Epispadias
PubMed: 37470562
DOI: 10.4103/ajps.ajps_172_21 -
Journal of Pediatric Urology Jun 2023Despite the proliferation of over 45 000 smartphone mobile health applications (MHAs), as far as we know, there is no MHA for those living with rare diseases such as...
GOALS
Despite the proliferation of over 45 000 smartphone mobile health applications (MHAs), as far as we know, there is no MHA for those living with rare diseases such as Bladder Exstrophy-Epispadias-Cloacal Exstrophy complex (BEEC). We hypothesized that an MHA could provide similar "on-demand" information and connectivity within health communities for patients with BEEC as they do for more common diseases. Thus, our primary goal was to create an MHA for patients and families affected by BEEC to provide them with important information about the condition and a format for them to connect with other affected patients and families. A secondary goal was to develop an adaptable MHA template for other rare diseases in the future.
METHODS
We began our app development by examining existing common-disease MHAs for thematic structure. We conducted an extensive literature search of PubMed and Google scholar for MHA development and existing MHAs related to BEEC, utilizing these search terms: mobile health applications, rare diseases, bladder exstrophy, and online health communities. Our app development team began with our clinical multidisciplinary team of pediatric urologists; a child psychiatrist; a patient/family mental health therapist; and a certified nurse practitioner. We hired a website engineer and a production team. All clinical members have extensive experience caring for children and families affected by BEEC. Additionally, clinical team members compiled lists of themes deemed relevant from these reviews and themes gleaned from their clinical experience that appear with some frequency or urgency and from the myriad of themes discussed within the literature for MHAs.
RESULTS
We found no existing rare disease MHAs in the literature or our search of app stores online. However, we derived basic app categories from existing MHA formats and the thematic content of all sources reviewed. These categories aligned with the groupings of our lists of clinical themes. Thus, we could subsume diverse themes within a broad categorical format: for example, child development (as "Psychological Development" in the app) or various clinical care options (as "Treatment"). This app structure became nine sections, as shown in. This format allows diverse information to be retrieved efficiently from broader categories. This app is being offered to affected families, healthcare providers, and individuals unrelated to where care is offered.
CONCLUSION
"We the BE" is the first MHA developed for a rare disease, BEEC. It has been published in a downloadable format for the general public at no cost. Further research is required to determine its efficacy for the BEEC community members; preliminary, unsolicited feedback from multiple users has been positive.
Topics: Humans; Child; Bladder Exstrophy; Epispadias; Rare Diseases; Mobile Applications
PubMed: 36959037
DOI: 10.1016/j.jpurol.2023.02.021