Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS): challenges in diagnosis and management.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare, congenital functional intestinal obstruction, characterised by megacystis (bladder distention in the absence of mechanical obstruction), microcolon and intestinal hypoperistalsis (dysmotility).We are reporting a case of a female child with normal antenatal course who presented with recurrent episodes of abdominal distension since the second day of life and underwent negative exploratory laparotomy on multiple occasions. She also had urinary retention with a grossly distended bladder, requiring drainage by clean intermittent catheterisation. Surgical procedures for bowel decompression, including gastrostomy and ileostomy, were carried out without success. Genetic analysis revealed a mutation in the human smooth muscle (enteric) gamma-actin gene (ACTG2 gene), clinching the diagnosis of MMIHS. The patient was managed with parenteral nutrition and prokinetic medications and tolerated jejunostomy feeds for a brief period before she succumbed to the illness.Female neonates or infants presenting with abdominal distension and dilated urinary tract should be investigated for MMIHS early on. A timely diagnosis will enable the early involvement of a multidisciplinary team to provide the best options available for management.

Genome-wide analysis identifies MYH11 compound heterozygous variants leading to visceral myopathy corresponding to late-onset form of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Megacystis-microcolon-hypoperistalsis-syndrome (MMIHS) is a rare and early-onset congenital disease characterized by massive abdominal distension due to a large non-obstructive bladder, a microcolon and decreased or absent intestinal peristalsis. While in most cases inheritance is autosomal dominant and associated with heterozygous variant in ACTG2 gene, an autosomal recessive transmission has also been described including pathogenic bialellic loss-of-function variants in MYH11. We report here a novel family with visceral myopathy related to MYH11 gene, confirmed by whole genome sequencing (WGS). WGS was performed in two siblings with unusual presentation of MMIHS and their two healthy parents. The 38 years-old brother had severe bladder dysfunction and intestinal obstruction, whereas the 30 years-old sister suffered from end-stage kidney disease with neurogenic bladder and recurrent sigmoid volvulus. WGS was completed by retrospective digestive pathological analyses. Compound heterozygous variants of MYH11 gene were identified, associating a deletion of 1.2 Mb encompassing MYH11 inherited from the father and an in-frame variant c.2578_2580del, p.Glu860del inherited from the mother. Pathology analyses of the colon and the rectum revealed structural changes which significance of which is discussed. Cardiac and vascular assessment of the mother was normal. This is the second report of a visceral myopathy corresponding to late-onset form of MMIHS related to compound heterozygosity in MYH11; with complete gene deletion and a hypomorphic allele in trans. The hypomorphic allele harbored by the mother raised the question of the risk of aortic disease in adults. This case shows the interest of WGS in deciphering complex phenotypes, allowing adapted diagnosis and genetic counselling.

Spontaneous rupture of bladder diverticulum with pseudo renal failure:A case report and literature review.

BACKGROUND: Spontaneous or non-traumatic bladder rupture is rare but can be life-threatening. Bladder rupture caused by a diverticulum is extremely rare, with only a few case reports in medical literature. CASE PRESENTATION: We report the case of a 32-year-old woman admitted to hospital complaints of abdominal pain, oliguria and ascites with no history of trauma. Laboratory tests revealed an elevated serum urea nitrogen(UN) level of 33.5 mmol/l and an elevated creatinine levels of 528 umol/l. X-ray cystography confirmed the rupture of a bladder diverticulum. Subsequent transurethral catheterization led to a prompt increase in urinary output, and serum creatinine level returned to 40 umol/l within 48 h. The patient was successfully treated with laparoscopic diverticulectomy. CONCLUSION: Clinicians should maintain a high level of suspicion for urinary bladder rupture in cases presenting with acute lower abdominal pain, urinary difficulties, and oliguria. When acute renal failure, complicated ascites, and an elevated peritoneal fluid creatinine or potassium level exceeding serum levels are observed, intraperitoneal urine leakage should be suspected without delay. This case emphasizes the importance of early diagnosis and intervention in managing this rare but serious condition.

Clinical and urodynamics outcomes in pediatric primary bladder diverticula: a comparative study.

OBJECTIVE: This study aimed to compare the effects of bladder diverticula smaller than 30 (SD) mm and larger than 30 mm (LD) on bladder functions and urodynamics. MATERIALS AND METHODS: Our retrospective analysis involved a cohort of 40 pediatric patients diagnosed with primary bladder diverticula. RESULTS: The predicted mean bladder capacity (MBC) was 197.7 ± 95.8 mL, whereas the observed MBC was lower at an average of 170.1 ± 79.6 mL. This indicates that the observed MBC was 88.2 ± 12.9% of the predicted value (percentage). The mean diverticula diameter recorded was 33 ± 19.5 mm, and the diverticula to MBC ratio were calculated to be 0.25 ± 0.18. The distribution of urinary tract infections (UTIs) differed significantly between the groups (p < 0.001). Upper UT dilatation was significantly more common in the LD group (60%, n = 12) than in the SD group (15%, n = 3) (p = 0.003). The mean detrusor pressure (P[detrusor]) was significantly higher in the LD group (137.2 ± 24.1 cm H2O) than in the SD group (63.9 ± 5.8 cm H2O) (p = 0.001). In addition, the mean peak flow rate (Qmax) was significantly higher in the SD group (20.7 ± 7.9 mL/s) compared to the LD group (12.7 ± 3.8 mL/s) (p < 0.001). CONCLUSION: Bladder diverticula size is a significant factor in the clinical presentation and management of primary bladder diverticula in pediatric patients.

OBJETIVO: Este estudio tuvo como objetivo comparar los efectos de los divertículos vesicales menores 30 mm (SD), mayores 30 mm (LD) en las funciones y urodinámica de vejiga. MATERIALES Y MÉTODOS: Nuestro análisis retrospectivo involucró una cohorte de 40 pacientes pediátricos diagnosticados con divertículos vesicales primarios. RESULTADOS: Capacidad vesical media predicha (MBC) fue de 197.7 ± 95.8 mL, mientras que MBC observada fue menor con promedio de 170.1 ± 79.6 mL. Esto indica que MBC observada fue del 88.2 ± 12.9% del valor predicho (porcentaje). Diámetro medio de divertículos registrados fue de 33 ± 19.5 mm, y se calculó que relación entre los divertículos y la MBC era de 0.25 ± 0.18. Distribución de infecciones del tracto urinario (ITU) difirió significativamente entre grupos (p < 0.001). Dilatación del tracto urinario superior (UT) fue significativamente más común en grupo LD (60%, n = 12) que en grupo SD (15%, n = 3) (p = 0.003). Presión media del detrusor (P[detrusor]) fue significativamente mayor en grupo LD (137.2 ± 24.1 cm H2O) que en grupo SD (63.9 ± 5.8 cm H2O) (p = 0.001). Además, tasa de flujo máximo promedio (Qmax) fue significativamente mayor en grupo SD (20.7 ± 7.9 mL/seg) en comparación con grupo LD (12.7±3.8 mL/seg) (p < 0.001). CONCLUSIONES: Tamaño de divertículos vesicales es factor significativo en presentación clínica, manejo de divertículos vesicales primarios en pacientes pediátricos.

Sagittal septum duplication of bladder and duplication of posterior urethra combined with congenital megacolon: a case report and literature review.

BACKGROUND: Duplication of the bladder with duplication of the posterior urethra is a relatively rare congenital malformation. Cases of sagittal septum duplication of the bladder with duplication of the posterior urethra have rarely been reported. Furthermore, the combination thereof with congenital megacolon is rare. CASE PRESENTATION: A 21-year-old male was admitted to our hospital because of frequent urination for two months. He presented to another hospital first with frequent urination and underwent computed tomography (CT) and testicular biopsy. Anti-inflammatory therapy was administered by the doctor to the patient. For further diagnosis and treatment, the patient went to the outpatient department in our hospital on June 6, 2022. After admission, the patient underwent ultrasound, CT, MRI, cystoscopy, and other related examinations and tests. The examination results suggested that the patient had duplication of the bladder with duplication of the posterior urethra. In addition, the patient's mother reported that he had suffered from long-term constipation with abdominal distension before the age of 5 years. At the time, he was admitted to the local hospital and was diagnosed with congenital megacolon based on the relevant examinations. After the patient was diagnosed with duplication of bladder and urethra, the doctor recommended surgical treatment to the patient. However, he considered that he only had frequent urination symptoms, and chose conservative treatment rather than to undergo surgical treatment. Thus, the doctor prescribed anti-inflammatory treatment. Four months later, the patient reported that frequent urination symptoms persisted, and was also considering fertility-related problems. The outpatient follow-up will be continued. CONCLUSIONS: In this article, we summarize the imaging findings of duplication of the bladder with duplication of the posterior urethra and propose the advantages and disadvantages of each type of imaging examination. We also review the relevant literature on cases of bladders with duplication of the posterior urethra. The related differential diagnosis is summarized, and the significance of guiding clinical treatment and diagnosis is discussed.

Chromosomal abnormalities associated with fetal megacystis.

Fetal megacystis has been reported to be associated with chromosomal abnormalities, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), obstructive uropathy, prune belly syndrome, cloacal anomalies, limb-body wall complex, amniotic band syndrome, anorectal malformations, VACTERL association (vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies and limb abnormalities) and fetal overgrowth syndrome such as Bechwith-Wiedemann syndrome and Sotos syndrome. This review provides an overview of chromosomal abnormalities associated with fetal megacystis which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal megacystis.

Syndromic and single gene disorders associated with fetal megacystis (I): Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS).

Fetal megacystis has been reported to be associated with chromosomal abnormalities, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), obstructive uropathy, prune belly syndrome, cloacal anomalies, limb-body wall complex, amniotic band syndrome, anorectal malformations, VACTERL association (vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies and limb abnormalities) and fetal overgrowth syndrome such as Bechwith-Wiedemann syndrome and Sotos syndrome. This review provides an overview of syndromic and single gene disorders associated with fetal megacystis which is useful for genetic counseling at prenatal diagnosis of fetal megacystis.

The utility of gene sequencing in identifying an underlying genetic disorder in prenatally suspected lower urinary tract obstruction.

OBJECTIVE: Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO-like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype-phenotype correlations. METHODS: A retrospective case series of suspected fetal LUTO positive for a molecular diagnosis was collected from five centers in the Fetal Sequencing Consortium. Demographics, sonograms, genetic testing including variant classification, and delivery outcomes were abstracted. RESULTS: Seven cases of initially prenatally suspected LUTO-positive for a molecular diagnosis were identified. In no case was the final diagnosis established as urethral obstruction that is, LUTO. All variants were classified as likely pathogenic or pathogenic. Smooth muscle deficiencies involving the bladder wall and interfering with bladder emptying were identified in five cases: MYOCD (2), ACTG2 (2), and MYH11 (1). Other genitourinary and/or non-genitourinary malformations were seen in two cases involving KMT2D (1) and BBS10 (1). CONCLUSION: Our series illustrates the value of molecular diagnostics in the workup of fetuses who present with prenatally suspected LUTO but who may have a non-LUTO explanation for their prenatal ultrasound findings.

Congenital lower urinary tract obstruction with spontaneous fetal bladder rupture due to posterior urethral valves: a case report.

BACKGROUND: Congenital lower urinary tract obstruction (LUTO) is a rare but significant condition affecting fetal urinary tract development. LUTO has a range of etiologies, with posterior urethral valves (PUV) being the most common cause. The prenatal diagnosis of LUTO plays a crucial role in recognizing the condition and guiding management decisions. Prenatal ultrasound serves as the primary tool for identifying LUTO, with key findings including megacystis, bladder wall thickening, oligohydramnios, hydronephrosis, and the 'keyhole sign' indicating dilatation of the posterior urethra. We present a case of congenital LUTO with a rare complication of spontaneous fetal bladder rupture and urinary ascites, treated by peritoneo-amniotic shunt placement. CASE PRESENTATION: A 27-year-old pregnant Caucasian women was referred at 28 weeks of pregnancy due to the presence of megacystis and bilateral hydronephrosis on routine ultrasound and suspicion of LUTO. Repeat ultrasound at 29 weeks showed significant fetal ascites, oligohydramnios and resolution of megacystis and hydronephrosis, after which diagnosis of spontaneous bladder rupture was made. Despite ascites aspiration and amnio-infusion, there was persistent ascites and oligohydramnios. A peritoneo-amniotic shunt was placed with resolution of ascites and normalization of the amniotic fluid volume. At 35 weeks, relapse of the megacystis was observed with bilateral pyelectasis and oligohydramnios, possibly due to healing of the bladder rupture, after which elective cesarean section was planned. Cystography confirmed spontaneous healing of the bladder rupture and the presence of posterior urethral valves, which were resected in the neonatal period with cold knife incision. Total follow-up of 8 years continued to show positive ultrasonographic results and good renal function, but the child suffers from bladder dysfunction, manifesting as overactive bladder disease. CONCLUSIONS: LUTO might lead to important renal dysfunction and pulmonary hypoplasia in case of increasing disease severity. Spontaneous bladder rupture might improve renal prognosis, acting as a pop-off mechanism by decompression of the urinary tract. However, fetal bladder rupture is rare and only few cases have been reported. Prenatal intervention can be considered for moderate or severe LUTO, but the benefit for long-term outcome remains uncertain and further studies are needed.

Inferior Vesical Fissure-A Rare Variant of Exstrophy Bladder: Case Report With Literature Review.

Exstrophy variants are uncommon developmental anomalies of the bladder; the variants involving only the bladder neck are extremely rare. There are only three case reports of inferior vesical fissure (IVF) to date, and usually it's uncommonly associated with other malformations. A combination of inferior vesical fistula (IVF) as an exstrophy variant with urethral atresia and anorectal malformation has not been described previously. We report a case of IVF in a 4-year-old male previously operated for anorectal malformation who was managed with fistula closure with bladder neck reconstruction of lay open of stenosed urethra. Recognition of the exstrophy variant is important because the treatment and prognosis are very different.

Bladder duplication in infant girls: role of imaging in two rare cases with variants of a complete sagittal septum.

Bladder duplication is an extremely rare congenital anomaly of the urinary system that is more frequent in boys; the literature is limited to case reports and case series. We describe two cases of bladder duplication in two infant girls with an uncommon variant of complete sagittal septum not included in the Abrahamson classification. The diagnosis was made using magnetic resonance urography, combining excellent anatomical information and static and dynamic evaluation of the urinary tract. The diagnostic information provided by MR-urography was confirmed on surgical exploration. These cases provide an opportunity for paediatric radiologists and urologists to learn more about bladder duplication and improve their diagnosis of this rare condition.

Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy.

Bladder exstrophy is a rare congenital malformation leaving the urinary bladder open in the midline of the abdomen at birth. There is a clear genetic background with chromosome aberrations, but so far, no consistent findings apart from 22q11-duplications detected in about 2%-3% of all patients. Some genes are implicated like the LZTR1, ISL1, CELSR3, and the WNT3 genes, but most are not explained molecularly. We have performed chromosomal microarray analysis on a cohort of 140 persons born with bladder exstrophy to look for submicroscopic chromosomal deletions and duplications. Pathogenic or possibly pathogenic microdeletions or duplications were found in 16 patients (11.4%) and further 9 with unknown significance. Two findings were in regions linked to known syndromes, two findings involved the same gene (MCC), and all other findings were unique. A closer analysis suggests a few gene networks that are involved in the pathogenesis of bladder exstrophy; the WNT-signaling pathway, the chromosome 22q11 region, the RIT2 and POU families, and involvement of the Golgi apparatus. Bladder exstrophy is a rare malformation and is reported to be associated with several chromosome aberrations. Our data suggest involvement of some specific molecular pathways.

Prenatal Detection of Vesico-Allantoic Cyst: Ultrasound and Autopsy Findings.

Introduction: The vesico-allantoic cyst is a communication between the fetal bladder and the allantois through a patent urachus.Case Report: We describe a 17-week of gestational age (WGA) fetus with a 40 x 30 mm vesico-allantoic cyst. At 19 WGA, ultrasound (US) detected bilateral dilatation of renal pelvis (5-6 mm), hydroureters, and hypospadias. Amniotic fluid, umbilical cord flow, and fetal biometry were regular. Due to uncertain prognosis, the parents opted for legal termination of pregnancy. Autopsy confirmed the prenatal findings, also revealing intestinal malrotation and Meckel's diverticulum.Discussion/Conclusion: Probably an initial urinary tract obstruction occurred, not yet affecting the amniotic fluid volume, but evident as pyelectasis. This case highlights the possibility that genito-urinary and intestinal anomalies may be found in association with the vesico-allantoic cyst.

Prenatally Ruptured Patent Urachus: A Case Report and Review of Literature.

Patent urachus is a type of urachal anomaly in which the urachus does not tail off but remains connected to the bladder in the umbilicus. The prevalence of patent urachus is very low. Herein, we report a case of patent urachus ruptured and exposed to amniotic fluid in utero. In this case, the size decreased after the second trimester, which was thought to be due to rupture in utero. After delivery, patent urachus was confirmed by inserting a foley catheter, which runs through a ruptured cyst on umbilical cord insertion. The day after delivery, the neonate underwent surgical excision of the urachal cyst and closing umbilicus. The mechanism of patent urachus rupture is unknown. As the fetus matures, it is thought that the higher intravesical pressure may affect the rupture of the cyst. Patent urachus could be ruptured in the uterus spontaneously, and surgical correction is needed. Therefore, prenatal differential diagnosis is important.

Linfoma extranodal de células B em vesícula urinária de um cão / Extranodal B-cell lymphoma in the urinary bladder in a dog

O linfoma é uma neoplasia de alta recorrência na rotina oncológica de medicina veterinária. Pode ser classificado em linfoma Hodgking-liked, com raros casos descritos somente em felinos,e não Hodgking, sendo este segundo o mais comum, subdividido em linfomas B ou T. O objetivo deste trabalho foi relatar a conduta clínica, diagnóstica e terapêutica do caso de uma cadela, de 12 anos, sem raça definida, que manifestava disúria, prostração, dor abdominal e ao exame físico a presença de uma massa na região hipogástrica. Esta foi diagnosticada com linfoma de grandes células por meio de exames de citologia e biópsia, com solicitação do exame de imunoistoquímica que confirmou linfoma difuso de grandes células de imunofenótipo B. Sem o envolvimento de nenhum outro sistema, classificou-se como linfoma primário de bexiga extranodal. O animal passou pelo tratamento quimioterápico realizando nove sessões de quimioterapia pelo protocolo de CHOP, contudo devido ao agravamento do caso a paciente veio a óbito cerca de sete meses após o diagnóstico da doença. O caso estudado foi de extrema importância para a compreensão de linfomas primários de bexiga em razão da escassez de informações relacionadas na literatura. Ainda, o cão é um excelente modelo experimental de linfomas não Hodgking em humanos, consequentemente compreender essa doença em cães promove a evolução conjunta da medicina humana.

Lymphoma is a highly recurrent rate neoplasm in the oncology routine of veterinary medicine. It can be classified into Hodgking-like, rarely described just in felines, and non-Hodgking lymphoma, the latter being the most commun, subdivided into B-cell lymphoma and T-cell lymphoma. The objective of this study was to report the clinical and therapeutic conduct within the diagnosis procedures of a 12-years-old female dog, mixed breed, who manifested dysuria, prostation, abdominal pain and on the physical examination a mass in the hypogastric region was noticed. This was diagnosed as a large cell lymphoma by means cytology and biopsy, also immunohistochemistry was required which confirmed the diffuse large cell lymphoma of immunophenotyping B. Without any other sistem envolved, the neoplasm was classified as primary urinary bladder lymphoma extranodal. The animal underwent chemotherapy, performing nine sessions according to the Madison protocol, however, due to the worsening of the case, the patient died about seven months after the diagnosis of the disease. This case was extremely importante for the understanding of primary urinary bladder lymphomas due to the scarcity of informations in the literature. Also, dog is an excellent experi,emtal model of non Hodgking lymphomas in humans, thus understandig this disease in dogs promotes the joint evolution of human medicine.

Iliac vein compression syndrome caused by a large bladder diverticulum: Case report and literature review.

Iliac vein compression syndrome is a rare disorder that causes oedema of one or both legs, with or without thrombosis. This current case report describes a 71-year-old male patient with left iliac vein compression caused by a bladder diverticulum that occurred secondary to chronic prostatic hyperplasia. The patient presented with left leg oedema without deep vein thrombosis. Contrast-enhanced computed tomography of the abdomen and pelvis, Doppler ultrasound imaging of the lower limb veins and magnetic resonance imaging helped confirm the diagnosis. The patient initially underwent urinary catheter placement, which relieved urinary retention and iliac vein compression. He subsequently underwent bladder diverticulectomy and transurethral prostatectomy. The postoperative clinical course was uneventful. During the 1.5-year follow-up, the patient did not have lower extremity oedema. Bladder diverticulum is an extremely rare cause of iliac vein compression syndrome, and only five such cases, including this one, have been reported to date. This article presents a literature review of these cases and a summary of the diagnosis and treatment experience.

Exstrophy-Epispadias Complex With Isolated Ectopic Bowel Segment: A Case Series and Literature Review.

OBJECTIVE: To present a case series of the exstrophy-epispadias complex (EEC) with isolated ectopic bowel segment (IEBS) with the literature review, highlighting the clinical findings and treatments. MATERIALS AND METHODS: We present 3 cases of bladder exstrophy (BE) with IEBS in our institute and reviewed the literature in PubMed with the terms "("bladder exstrophy" OR "epispadias") AND ("visceral sequestration" OR "sequestered" OR "ectopic bowel")." RESULTS: There were 2 males and 1 female. The IEBS was detected by physical examination in 2 cases and by ultrasonography in another one. All cases were BE accompanying with lower abdominal mass which adhered to the bladder wall but was separated from the digestive system. All cases underwent the IEBS excision and BE repair simultaneously. Pathological result of IEBS suggested the histological structures of colon. There were totally 13 cases of EEC with IEBS reported in the literature, including 2 (15%) epispadias, 9 (69%) covered BE, 1 (8%) duplicate BE and 1 (8%) classic bladder exstrophy. Although their clinical manifestations were various, IEBS excision were safely conducted in all cases. CONCLUSION: EEC with IEBS is an extremely rare congenital malformation. Physical and imaging examinations are important for diagnoses. Surgical excision is safe and effective for managing IEBS.

[Ectopic duodenal varices as a cause of difficult diagnosis of bleeding in extrahepatic portal hypertension]. / Varikoznye veny dvenadtsatiperstnoi kishki kak prichina «trudno¼ diagnostiruemogo krovotecheniya pri vnepechenochnoi portal'noi gipertenzii.

Bleeding from ectopic varicose veins is a rare life-threatening cause of upper gastrointestinal hemorrhage. Alberti first described duodenal varices in 1931. According to the literature, incidence of duodenal varicose veins in patients with portal hypertension is 1-3% of all varicose veins. Bleeding from duodenal varices makes up 17% of all bleedings from other ectopic varices. Mortality in these patients may be up to 40%. The causes are delayed diagnosis, technical difficulties in endoscopic therapeutic procedures (sclerotherapy, endoscopic ligation), as well as ineffective Blackmore tube for hemorrhage in distal stomach and bowel. We report a rare case of upper gastrointestinal bleeding from ectopic duodenal varices.

Narrowing the chromosome 22q11.2 locus duplicated in bladder exstrophy-epispadias complex.

INTRODUCTION: Bladder exstrophy-epispadias complex (BEEC) comprises a spectrum of anterior midline congenital malformations, involving the lower urinary tract. BEEC is usually sporadic, but families with more than one affected member have been reported, and a twin concordance study supported a genetic contribution to pathogenesis. Moreover, diverse chromosomal aberrations have been reported in a small subset of individuals with BEEC. The commonest are 22q11.2 microduplications, identified in approximately 3% of BEEC index cases. OBJECTIVES: We aimed to refine the chromosome 22q11.2 locus, and to determine whether the encompassed genes are expressed in normal developing and mature human urinary bladders. RESULTS: Using DNA from an individual with CBE, the 22q11.2 duplicated locus was refined by identification of a maternally inherited 314 kb duplication (chr22:21,147,293-21,461,017), as depicted in this image. Moreover, the eight protein coding genes within the locus were found to be expressed during normal developing and mature bladders. To determine whether duplications in any of these individual genes were associated with CBE, we undertook copy number analyses in 115 individuals with CBE without duplications of the whole locus. No duplications of individual genes were found. DISCUSSION: The current study has refined the 22q11.2 locus associated with BEEC and has shown that the eight protein coding genes are expressed in human bladders both during antenatal development and postnatally. Nevertheless, the precise biological explanation as to why duplication of the phenocritical region of 22q11 confers increased susceptibility to BEEC remains to be determined. The fact that individuals with CBE without duplications of the whole locus also lacked duplication of any of the individual genes suggests that in individuals with BEEC and duplication of the 22q11.2 locus altered dosage of more than one gene may be important in BEEC etiology. CONCLUSIONS: The study has refined the 22q11.2 locus associated with BEEC and has shown that the eight protein coding genes within this locus are expressed in human bladders.