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.

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.

Transparaumbilical Intravariceal Sclerotherapy for Duodenal Varices Using Outflow Embolization.

A 55-year-old patient was admitted for variceal treatment, a complication of chronic portal hypertension and liver cirrhosis. Imaging studies revealed prominent duodenal varices, the pancreaticoduodenal vein as its afferent pathway, a drainer vessel into the inferior vena cava, and a paraumbilical vein. We successfully performed complete obliteration of the varix, including its afferent and efferent vessels, via the paraumbilical vein approach.

Congenital duodenal web causing partial obstruction with recurrent vomiting and abdominal distention in a toddler boy: a case report.

BACKGROUND: The duodenal web is a thin, elongated, web-like structure that is one of the factors contributing to duodenal obstruction. Only 100 cases have been reported in the literature. We present a 2.5-year-old cachectic Afghan child who did not have any overt signs and symptoms of intestinal obstruction, like recurrent vomiting, abdominal distention, and weight loss. The web was discovered near the intersection of the third and fourth portions, which is an uncommon location for the duodenal web. The late presentation of congenital duodenal web with partial obstruction is rare but well-known and has been reported in this case. CASE PRESENTATION: A 2.5-year-old cachectic Afghan child who had recurrent vomiting and experienced abdominal distention was brought to Maiwand Teaching Hospital from the Jabelsuraj region of Parwan province. The patient was suffering from unusual signs and symptoms like recurrent vomiting, abdominal distention, weight loss, and constipation. The diagnosis of these anomalies was established by a detailed history, clinical features, and abdominal CT scan. In the computerized tomography scanning (CT-Scan) image reported, there was a web with stenosis and partial obstruction in the distal aspect of the third-to-fourth portion of the duodenum. After preoperative stabilization, the child was taken for surgery. The abdomen was opened by a right upper abdominal transverse incision. After web resection and duodenoplasty, the patient was shifted to the recovery room in satisfactory condition. The child was allowed to feed after 8 days, which he tolerated well. CONCLUSION: Congenital duodenal web with partial obstruction is typically observed in the second and third years of life. It is suspected in patients with recurrent vomiting, abdominal distention, weight loss, and constipation. Partial obstruction may not have an overt presentation, making it a challenging diagnosis for general practitioners. Abdomen X-ray and CT scan usually confirm the diagnosis, and successful surgical intervention is recommended.

Ectopic Opening of Common Bile Duct to Duodenal Bulb: A Single Tertiary Center Experience.

BACKGROUND: The ectopic opening of the common bile duct(CBD) into the duodenal bulb is a rare biliary anomaly. The study aimed to reveal the experience with clinical and endoscopic outcomes in these patients. MATERIALS AND METHODS: This study was conducted on 57 consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for ectopic opening of the CBD into the duodenal bulb at our institution between 2010 and 2020. RESULTS: The median age was 59 years (49 males). A total of 146 ERCP procedures were performed (once in 26 patients and 2 or more times in 31 patients). Ten patients had a history of unsuccessful ERCP in an external center. The median follow-up time was 14.6 months. All patients had a slit-like opening of the CBD into the duodenal bulb, apical stenosis, and hook-shaped distal CBD. ERCP findings were CBD stone or dilatation in 55 patients and post-cholecystectomy biliary leakage in 2 patients. Balloon dilatation was performed for apical stenosis in 7 patients and distal CBD stenosis in 26 patients. During the first ERCP session, biliary stent/nasobiliary drainage was placed in 37 patients, and CBD stones were extracted in 19 patients without stenting. Biliodigestive anastomosis was applied to 13 patients, 5 of whom had recurrent cholangitis, 7 required recurrent ERCP, and one was due to the technical difficulty of ERCP. CONCLUSIONS: Ectopic biliary opening should be remembered if the papilla cannot be seen in its usual place in a patient with apical stenosis. ERCP should be performed in experienced hands, and surgery should be considered in the need for recurrent ERCP.

Endoscopic treatment of periampullary duodenal duplication cyts in an 18-month-old girl.

BACKGROUND: Duodenal duplication cysts (DDC) are rare congenital anomalies of the gastrointestinal tract and periampullary localization with anatomical variants including biliary and pancreatic duct anomalies remains a surgical challenge. Endoscopic treatment of the periampullary DDC (PDDC) communicating with the pancreaticobiliary duct in an 18-month-old girl is presented to discuss the endoscopic treatment options in children. CASE: An 18-month-old girl with a normal prenatal ultrasound (US) was asymptomatic until complaining of abdominal pain and vomiting at 10-months of age. Abdominal US revealed a 1.8 × 2 cm cystic mass adjacent to the second part of the duodenum. The amylase and lipase levels were slightly increased while she was symptomatic. Magnetic resonance cholangiopancreaticography (MRCP) showed a thick cyst wall measuring 1.5 × 2 cm at the second part of the duodenum, consistent with DDC that was suspected to be communicating with the common bile duct. Upper gastrointestinal endoscopy confirmed a bulging cyst in the duodenum lumen. The puncture and injection of the cyst with contrast material confirmed the communication of the duplication cyst with the common bile duct. The unroofing of the cyst was performed with endoscopic cautery. The biopsy obtained from the cystic mucosa revealed normal intestinal histology. Oral feeding was initiated six hours after the endoscopy. The patient has been followed for the last 8 months uneventfully. CONCLUSIONS: Endoscopic treatment of PDDC with various anatomical variants can be considered an alternative to surgical excision in children.

[A 19-year-old female patient with acute pancreatitis of unusual cause]. / 19-jährige Patientin mit akuter Pankreatitis ungewöhnlicher Ursache.

We report the case of a 19-year-old woman with abdominal pain and diarrhea. The diagnosis of acute pancreatitis could be made clinically and through laboratory tests. The cause was a duodenal duplication cyst in the area of the papilla, which was initially relieved endoscopically. Once the acute inflammation had healed, the cyst was resected endoscopically to prevent recurrence and the increased risk of malignancy. Duodenal duplication cysts in the papillary area are a very rare (congenital) cause of acute pancreatitis. If a cyst is present in the area of the duodenal wall, however, this differential diagnosis should be considered. Resection is indicated for therapy.

[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.

[Factors associated with the survival of fetuses with a prenatal diagnosis of megabladder]. / Factores asociados a sobrevida de fetos con diagnóstico prenatal de megavejiga.

The presence of fetal megacystis in a renal ultrasound may suggest a mechanical or functional bladder outlet obstruction, an uncommon condition with a poor outcome. OBJECTIVE: To determine prog nostic factors in fetuses with prenatal diagnosis of megacystis. PATIENTS AND METHOD: Retrospective study carried out between 2003 and 2018 in the Orient Perinatal Reference Center (CERPO), Uni versity of Chile. Prenatal and postnatal data were analyzed, as well as etiology, pulmonary hypoplasia, medical and surgical treatment, mortality, renal function, and need for renal replacement therapy. The primary variable analyzed was survival at one year, and the secondary ones were renal function and predictors of survival. Statistical analysis was performed using the Mann-Whitney U tests or Fisher test, and a p < 0.05 was considered statistically significant. RESULTS: Twenty-five fetuses with prenatal diagnosis of megacystis were included. 52% of them presented oligohydramnios and 84% showed renal anomalies. Vesicocentesis was performed in 15 fetuses and vesicoamniotic shunt was performed in 5 cases. There were 6 intrauterine fetal deaths (24%) and, among the 19 live births, 9 died soon after birth (36%) and 1 died in the post-neonatal period due to a non-nephron-urological cause. Nine newborns survived by one year of age (36%), seven of them with associated nephron- urological anomaly, and two were healthy patients. Two patients developed chronic kidney disease. The presence of pulmonary hypoplasia was the only factor associated with increased perinatal mor tality (p<0.05) secondary to oligohydramnios in all cases. Oligohydramnios was not identified as a prognostic factor in this study. CONCLUSIONS: The prenatal diagnosis of megacystis comprises a wide spectrum of pathologies including conditions with a high perinatal mortality rate to healthy fetuses with transient enlarged bladder without nephron-urological pathology. The only factor associated with increased perinatal mortality was pulmonary hypoplasia.

A rare case of duodenal variceal bleeding due to extrahepatic portal vein obstruction successfully treated with endoscopic injection sclerotherapy.

Primary extra-hepatic portal vein obstruction (EHPVO) is a disease that develops ectopic varices due to portal hypertension and obstruction of the portal vein. Since bleeding from ectopic varices is life-threatening, the management of ectopic varices is important for patients with primary EHPVO. Here, we report a case of duodenal variceal bleeding in a patient with primary EHPVO. A 39-year-old man was diagnosed with F2-shaped duodenal varices (DV) due to primary EHPVO and was first treated with endoscopic variceal ligation for temporary hemostasis. We then performed angiography to understand the detailed hemodynamics and subsequently conducted endoscopic injection sclerotherapy (EIS) with a sclerosing agent containing N-butyl-2-cyanoacrylate for further hemostasis. After the treatment, dynamic computed tomography and endoscopic ultrasound revealed that the blood flow to the causative DV disappeared, although the DV itself remained. The patient was discharged without any re-bleeding or adverse events. Since treatment for DV due to primary EHPVO differs depending on hemodynamics (hepatofugal or hepatopetal blood flow), evaluating detailed hemodynamics for optimal treatment selection is crucial. Although EIS for this patient was not a radical treatment, it was effective in managing acute bleeding from the DV. This case will serve as a reference for successful treatment in future cases.

Dual duodenojejunostomies in the repair of megaduodenum, duodenal stenosis and prior missed diagnosis of annular pancreas.

Duodenal stenosis and atresia are some of the most common forms of congenital bowel obstruction. The gold standard approach to treatment is duodenoduodenostomy, while rare, gastrojejunostomy and duodenojejunostomies may still be used. We report a case of a 7-year-old male presenting with annular pancreas with duodenal stenosis that was diagnosed at birth as primary duodenal atresia and repaired by gastrojejunostomy with a Braun enteroenterostomy. Through successful reoperation with dual duodenojejunostomy and subsequent management, we treated the sequelae of the initial repair, including megaduodenum. Regions of duodenal obstruction must have direct anastomotic repair to prevent subsequent issues related to dysmotility. Otherwise, further surgical intervention and long-term medical management, such as the novel strategy reported, may be necessary.

Megacystis in the first trimester of pregnancy: Prognostic factors and perinatal outcomes.

OBJECTIVE: To determine whether bladder size is associated with an unfavorable neonatal outcome, in the case of first-trimester megacystis. MATERIALS AND METHODS: This was a retrospective observational study between 2009 and 2019 in two prenatal diagnosis centers. The inclusion criterion was an enlarged bladder (> 7 mm) diagnosed at the first ultrasound exam between 11 and 13+6 weeks of gestation. The main study endpoint was neonatal outcome based on bladder size. An adverse outcome was defined by the completion of a medical termination of pregnancy, the occurrence of in utero fetal death, or a neonatal death. Neonatal survival was considered as a favorable outcome and was defined by a live birth, with or without normal renal function, and with a normal karyotype. RESULTS: Among 75 cases of first-trimester megacystis referred to prenatal diagnosis centers and included, there were 63 (84%) adverse outcomes and 12 (16%) live births. Fetuses with a bladder diameter of less than 12.5 mm may have a favorable outcome, with or without urological problems, with a high sensitivity (83.3%) and specificity (87.3%), area under the ROC curve = 0.93, 95% CI (0.86-0.99), p< 0.001. Fetal autopsy was performed in 52 (82.5%) cases of adverse outcome. In the 12 cases of favorable outcome, pediatric follow-up was normal and non-pathological in 8 (66.7%). CONCLUSION: Bladder diameter appears to be a predictive marker for neonatal outcome. Fetuses with smaller megacystis (7-10 mm) have a significantly higher chance of progressing to a favorable outcome. Urethral stenosis and atresia are the main diagnoses made when first-trimester megacystis is observed. Karyotyping is important regardless of bladder diameter.

Prenatal diagnosis of megaduodenum using ultrasound: a case report.

BACKGROUND: Congenital megaduodenum is a rare disorder; however, its prenatal diagnosis has not been reported previously. We report the case of an abdominal cystic mass in a fetus that was later diagnosed as megaduodenum. CASE PRESENTATION: An abdominal cystic mass was found during ultrasonography of a fetus at 11 weeks of gestation. The mass progressively enlarged with gestation. The amniotic fluid volume decreased and then returned to normal. During the last prenatal ultrasound examination, the mass was observed communicating with the stomach; therefore, duodenal dilation was suspected. Finally, the patient was diagnosed with megaduodenum caused by a developmental defect in the nerve plexus. CONCLUSIONS: Congenital megaduodenum is a differential diagnosis of massive fetal abdominal cystic masses. Ultrasound examinations of such masses communicating with the stomach may help determine the diagnosis.

Z-scores of fetal bladder size for antenatal differential diagnosis between posterior urethral valves and urethral atresia.

OBJECTIVE: To construct reference values for fetal urinary bladder distension in pregnancy and use Z-scores as a diagnostic tool to differentiate posterior urethral valves (PUV) from urethral atresia (UA). METHODS: This was a prospective cross-sectional study in healthy singleton pregnancies aimed at constructing nomograms of fetal urinary bladder diameter and volume between 15 and 35 weeks' gestation. Z-scores of longitudinal bladder diameter (LBD) were calculated and validated in a cohort of fetuses with megacystis with ascertained postnatal or postmortem diagnosis, collected from a retrospective, multicenter study. Correlations between anatomopathological findings, based on medical examination of the infant or postmortem examination, and fetal megacystis were established. The accuracy of the Z-scores was evaluated by receiver-operating-characteristics (ROC)-curve analysis. RESULTS: Nomograms of fetal urinary bladder diameter and volume were produced from three-dimensional ultrasound volumes in 225 pregnant women between 15 and 35 weeks of gestation. A total of 1238 urinary bladder measurements were obtained. Z-scores, derived from the fetal nomograms, were calculated in 106 cases with suspected lower urinary tract obstruction (LUTO), including 76 (72%) cases with PUV, 22 (21%) cases with UA, four (4%) cases with urethral stenosis and four (4%) cases with megacystis-microcolon-intestinal hypoperistalsis syndrome. Fetuses with PUV showed a significantly lower LBD Z-score compared to those with UA (3.95 vs 8.83, P < 0.01). On ROC-curve analysis, we identified 5.2 as the optimal Z-score cut-off to differentiate fetuses with PUV from the rest of the study population (area under the curve, 0.84 (95% CI, 0.748-0.936); P < 0.01; sensitivity, 74%; specificity, 86%). CONCLUSIONS: Z-scores of LBD can distinguish reliably fetuses with LUTO caused by PUV from those with other subtypes of LUTO, with an optimal cut-off of 5.2. This information should be useful for prenatal counseling and management of LUTO. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.