LUMBAR syndrome-OEIS complex overlap: A case series and review.

We present three new and six published infants with overlapping features of LUMBAR syndrome (lower body hemangioma, urogenital anomalies, spinal cord malformations, bony deformities, anorectal/arterial anomalies and renal anomalies) and OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects), also known as cloacal exstrophy. OEIS is included under the recently proposed umbrella coined recurrent constellations of embryonic malformations (RCEMs). The RCEMs represent a phenotypically overlapping spectrum of rare disorders of caudal dysgenesis with unknown cause but likely shared pathogenesis. It has recently been proposed that LUMBAR be considered an RCEM. This report of infants with combined features of OEIS and LUMBAR is the first to demonstrate an overlap between LUMBAR and another RCEM, which supports LUMBAR's inclusion within the RCEM spectrum.

Helicobacter monodelphidis sp. nov. and Helicobacter didelphidarum sp. nov., isolated from grey short-tailed opossums (Monodelphis domestica) with endemic cloacal prolapses.

In a search for potential causes of increased prolapse incidence in grey short-tailed opossum colonies, samples from the gastrointestinal tracts of 94 clinically normal opossums with rectal prolapses were screened for Helicobacter species by culture and PCR. Forty strains of two novel Helicobacter species which differed from the established Helicobacter taxa were isolated from opossums with and without prolapses. One of the Helicobacter species was spiral-shaped and urease-negative whereas the other Helicobacter strain had fusiform morphology with periplasmic fibres and was urease-positive. 16S rRNA gene sequence analysis revealed that all the isolates had over 99 % sequence identity with each other, and were most closely related to Helicobacter canadensis. Strains from the two novel Helicobacter species were subjected to gyrB and hsp60 gene and whole genome sequence analyses. These two novel Helicobacter species formed separate phylogenetic clades, divergent from other known Helicobacter species. The bacteria were confirmed as novel Helicobacter species based on digital DNA-DNA hybridization and average nucleotide identity analysis of their genomes, for which we propose the names Helicobacter monodelphidis sp. nov. with the type strain MIT 15-1451T (=LMG 29780T=NCTC 14189T) and Helicobacter didelphidarum sp. nov with type strain MIT 17-337T (=LMG 31024T=NCTC 14188T).

Cloacal Diseases in Companion Parrots: A Retrospective Study of 43 Cases (2012-2018).

Cloacal disease is considered a common presenting complaint in companion parrots. The purpose of this study was to better characterize the prevalence of cloacal disease within a population of owned psittacine birds. Medical records of all owned parrots presented to an exotic animal specialty service between July 2012 and January 2018 were retrospectively reviewed for the presence of cloacal disease. Cloacal disease was identified in 43 of 1137 cases (3.8%). Cockatoos presented with cloacal disease significantly more often than other psittacine groups (P < .001). Female parrots presented with cloacal disease significantly more often than males and unsexed birds (P < .001). Cockatoos with cloacal disease predominantly presented with prolapse of the cloaca itself (P = .006). There was no significant difference in outcome based on taxonomic group, sex, or primary cloacal pathology. Prospective studies with parrot species are encouraged to have an increased understanding of the behavioral and medical conditions that result in cloacal disease. These studies would hopefully facilitate the development of better treatment options for this relatively common disease presentation.

Diagnosis and Surgical Repair of an Acute Abdominal Wall Hernia and Partial Cloacal Strangulation in a Yellow-Naped Amazon Parrot (Amazona auropalliata).

A 38-year-old female, intact yellow-naped Amazon parrot (Amazona auropalliata) presented with an acute swelling along the ventrocaudal body wall, hematochezia, and tenesmus. Physical examination identified a defect in the ventral body wall. Bimodal pain management was initiated at presentation and hematochezia and tenesmus resolved. Radiographic imaging and contrast fluoroscopy identified a partial cloacal strangulation. An exploratory celiotomy was performed. Adhesions to the body wall were identified and broken down, the cloacal position was corrected, and the abdominal musculature repaired. Contrast fluoroscopy performed 72 hours after surgery confirmed normal positioning of the cloaca. Follow-up examinations documented proper postoperative healing of the hernia repair and maintenance of visibly normal passage of droppings. Although various abdominal hernias have been described in birds, this case demonstrates an unreported variation involving partial cloacal strangulation in a parrot.

Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal mesenchyme.

The vesico-ureteric junction (VUJ) forms through a complex developmental program that connects the primordium of the upper urinary tract [the nephric duct (ND)] with that of the lower urinary tract (the cloaca). The signals that orchestrate the various tissue interactions in this program are poorly understood. Here, we show that two members of the EphA subfamily of receptor tyrosine kinases, EphA4 and EphA7, are specifically expressed in the mesenchyme surrounding the caudal ND and the cloaca, and that Epha4(-/-);Epha7(+/-) and Epha4(-/-);Epha7(-/-) (DKO) mice display distal ureter malformations including ureterocele, blind and ectopically ending ureters with associated hydroureter, megaureter and hydronephrosis. We trace these defects to a late or absent fusion of the ND with the cloaca. In DKO embryos, the ND extends normally and approaches the cloaca but the tip subsequently looses its integrity. Expression of Gata3 and Lhx1 and their downstream target Ret is severely reduced in the caudal ND. Conditional deletion of ephrin B2 from the ND largely phenocopies these changes, suggesting that EphA4/EphA7 from the pericloacal mesenchyme signal via ephrin B2 to mediate ND insertion. Disturbed activity of this signaling module may entail defects of the VUJ, which are frequent in the spectrum of congenital anomalies of the kidney and the urinary tract (CAKUT) in human newborns.

Mutations of MYH14 are associated to anorectal malformations with recto-perineal fistulas in a small subset of Chinese population.

BACKGROUND: Anorectal malformations (ARMs) are among the most commonly congenital abnormalities of distal hindgut development, ranging from anal stenosis to anal atresia with or without fistulas and persistent cloaca. The etiology remains elusive for most ARM cases and the majority of genetic studies on ARMs were based on a candidate gene approach. MATERIALS AND METHODS: In all eight family members of a non-consanguineous Chinese family, we performed whole-exome sequencing. Subsequently, exome sequencing of MYH14 in 72 unrelated probands with ARMs was performed. The accurate distribution of non-muscle myosin II heavy chain (NMHC II) was investigated by immunohistochemistry in serial sagittal sections of E11.5-13.5 mouse cloacal regions. RESULTS: A homozygous mutation in MYH14 was identified in the two siblings of family 1. Compound heterozygous MYH14 changes were identified in an unrelated individual. Immunohistochemical analysis suggest stronger NMHC IIC localization in the epithelium of the murine embryonic cloaca, urorectal septum and hindgut compared with another two NMHC II isoforms. CONCLUSION: This is the first identification of mutations in MYH14 as a cause of ARMs. The stronger localization of NMHC IIC in E11.5-13.5 mouse cloacal regions further supports the role of MYH14 in anorectal development.

Fibronectin glomerulopathy complicated with persistent cloaca and congenital esophageal atresia: a case report and literature review.

BACKGROUND: Fibronectin glomerulopathy is a rare, inherited, autosomal dominant, glomerular disease characterized by proteinuria, microscopic hematuria, hypertension, massive glomerular deposits of fibronectin, and slow progression to end-stage renal failure. Because the incident of fibronectin glomerulopathy is extremely low, the pathophysiology, genetic abnormalities, epidemiology, and mechanisms remain to be elucidated. CASE PRESENTATION: We report a 21-year-old woman with fibronectin glomerulopathy, who had been diagnosed with persistent cloaca and congenital esophageal atresia at birth. She developed proteinuria and hematuria 7 months before admission. Urinary protein and serum creatinine levels were 3.38 g/gCr and 0.73 mg/dL. Renal biopsy showed severe mesangial widening due to massive deposits, which was positive periodic acid-Schiff and negative methenamine silver. Immunostaining was negative for immunoglobulin but positive for fibronectin. Electron microscopy showed diffuse mesangial granular deposits. Thus she was diagnosed with fibronectin glomerulopathy, despite a negative family history of kidney disease and lack of any known missense mutations of fibronectin 1 gene. CONCLUSION: We report a patient who developed fibronectin glomerulopathy during the clinical course of extremely rare congenital malformations, including persistent cloaca and congenital esophageal atresia. We describe a case of this condition in detail and summarize the 75 case reports of fibronectin glomerulopathy.

Primary mucinous carcinoma of the vulva with signet ring cells deriving from the cloaca.

Vulvar neoplasias are rarely encountered lesions at female genital tract, regardless if they are primary or metastatic. Presence of signet ring cells in a tumour at female genito-urinary tract is highly suggestive of a metastatic lesion particularly from a gastrointestinal tumour. Here the authors present a case of vulvar carcinoma with signet ring cells with an undetermined primary site possibly originating from embryonic cloaca.

UNSEDATED COMPUTED TOMOGRAPHY FOR DIAGNOSIS OF PELVIC CANAL OBSTRUCTION IN A LEOPARD GECKO (EUBLEPHARIS MACULARIUS).

An adult leopard gecko ( Eublepharis macularius ) presented for lethargy, hyporexia, weight loss, decreased passage of waste, and a palpable caudal coelomic mass. Computed tomography showed a heterogeneous hyperattenuating (∼143 Hounsfield units) structure within the right caudal coelom. The distal colon-coprodeum lumen or urinary bladder was hypothesized as the most likely location for the heterogeneous structure. Medical support consisted of warm water and lubricant enema, as well as a heated environment. Medical intervention aided the passage of a plug comprised centrally of cholesterol and urates with peripheral stratified layers of fibrin, macrophages, heterophils, and bacteria. Within 24 hr, a follow-up computed tomography scan showed resolution of the pelvic canal plug.

Cloacal Prolapse in Raptors: Review of 16 Cases.

Sixteen cases of cloacal prolapse in raptors were reviewed in this study. Colonic prolapse was the most common presentation (56% of cases). Red-tailed hawks ( Buteo jamaicensis ) were overrepresented, comprising 66% of colonic prolapse cases. In cases of colonic prolapse, postsurgical stricture formation was a commonly identified complication after resection and anastomosis of the colon. A novel technique was used in 2 cases of colonic prolapse, in which sterile, semirigid rubber tubing was placed in the distal colon and removed per-cloaca at the end of the procedure; this facilitated a secure, fluid-tight anastomosis while maintaining sufficient intestinal lumen. Oviductal prolapse (31% of cases) was associated with the most guarded prognosis (40% treatment success). Cloacoliths were treated successfully in 2 birds (13% of cases) by minimally invasive per-cloacal manual removal.

RENAL AND CLOACAL CRYPTOSPORIDIOSIS (CRYPTOSPORIDIUM AVIAN GENOTYPE V) IN A MAJOR MITCHELL'S COCKATOO (LOPHOCHROA LEADBEATERI).

A 7-yr-old male Major Mitchell's cockatoo (Lophochroa leadbeateri) presented with a recent history of lethargy and anorexia. Physical examination revealed poor body condition and cloacal prolapse. Abnormalities on serum chemistry included severe hyperuricemia and hyperphosphatemia with a low calcium-to-phosphorus ratio. Symptomatic treatment was initiated including intravenous fluids and antibiotics. The bird continued to decline and died within a few days. Visceral gout and renal and cloacal pathology were observed on gross necropsy. Histopathology revealed chronic inflammation within the kidney, ureter, and cloaca in association with protozoal organisms and an invasive cloacal adenocarcinoma tumor. The location and morphology was consistent with Cryptosporidium sp., confirmed by immunohistochemistry and molecular testing. Direct sequencing identified Cryptosporidium avian genotype V. To the author's knowledge, this is the first reported infection of Cryptosporidium avian genotype V associated with clinical disease in birds and the first renal Cryptosporidium infection in a psittacine.

Comparison of vaccine subpopulation selection, viral loads, vaccine virus persistence in trachea and cloaca, and mucosal antibody responses after vaccination with two different Arkansas Delmarva Poultry Industry -derived infectious bronchitis virus vaccines.

Factors responsible for the persistence of Arkansas Delmarva Poultry Industry (ArkDPI)-derived infectious bronchitis vaccines in commercial flocks and the high frequency of isolation of ArkDPI-type infectious bronchitis viruses in respiratory cases are still unclear. We compared dynamics of vaccine viral subpopulations, viral loads, persistence in trachea and cloaca, and the magnitude of infectious bronchitis virus (1BV)-specific antibody induction after vaccination with two commercial ArkDPI-derived Arkansas (Ark) serotype vaccines. One of the vaccines (coded vaccine B) produced significantly higher vaccine virus heterogeneity in vaccinated chickens than the other vaccine (coded A). Chickens vaccinated with vaccine B had significantly higher viral loads in tears at 5 days postvaccination (DPV) than those vaccinated with vaccine A. Vaccine B also induced a significantly higher lachrymal immunoglobulin M response at 11 DPV, an earlier peak of IBV-specific lachrymal immunoglobulin A, and higher serum antibodies than vaccine A. In addition, a significantly higher proportion of birds vaccinated with vaccine B had vaccine virus detected in the trachea at 20 DPV than those vaccinated with vaccine A. Furthermore, the virus detected at 20 DPV in most of the chickens vaccinated with vaccine B was a single specific subpopulation (subpopulation 4) selected from multiple vaccine subpopulations detected earlier at 5 and 7 DPV in the same chickens. On the other hand, a higher proportion of chickens vaccinated with vaccine A had virus detected in cloacal swabs at 20 DPV. Thus we found differences in mucosal antibody induction and selection and persistence of vaccine viruses between two ArkDPI-derived vaccines from different manufacturers. The higher vaccine virus heterogeneity observed in chickens vaccinated with vaccine B compared with those vaccinated with vaccine A may be responsible for these differences. Thus the high frequency of Ark IBV viruses in the field may be due to the inherent ability of some ArkDPI-derived vaccine viruses to be selected and persist in vaccinated chickens. Vaccine virus persistence may offer genetic material for recombination or may undergo mutations with the potential to result in increased virulence.

Cloacal dysgenesis diagnosis by prenatal ultrasound and MRI.

Cloacal malformations are a spectrum of congenital pelvic malformations that result from abnormal cloacal division during early embryogenesis. Depending on the timing of the developmental arrest, a spectrum of abnormalities can result, ranging from urogenital sinus malformations to cloacal dysgenesis. This case highlights the unique imaging features of cloacal dysgenesis, which is an extremely rare variant of this malformation spectrum. This variant is also the most severe manifestation of the cloacal malformation spectrum.

Cloacolithiasis and intestinal lymphosarcoma in an African black-footed penguin (Spheniscus demersus).

A 13-yr-old male African black-footed penguin (Spheniscus demersus) presented thrice over 7 mo with gastrointestinal obstruction secondary to cloacolithiasis. Clinical signs consistently resolved with cloacolith removal and supportive care. However, 10 mo after initial presentation, it presented with similar signs, plus significant weight loss. No cloacolith was found, and it subsequently died. Significant gross findings included bilateral cecal masses, colonic perforation, and marked secondary coelomitis, multifocal tan to pale hepatic nodules, and pale kidneys with miliary white foci. Histopathologic diagnoses were intestinal lymphosarcoma with hepatic and renal metastases, secondary intestinal rupture, and subacute severe bacterial coelomitis. To the authors' knowledge, this is the first full report of either cloacolithiasis or lymphosarcoma in a penguin.

Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish.

NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remained elusive. Here we demonstrate that nephrocystin-4 is required for normal cloaca formation during zebrafish embryogenesis. Time-lapse imaging of the developing zebrafish pronephros revealed that tubular epithelial cells at the distal pronephros actively migrate between the yolk sac extension and the blood island towards the ventral fin fold to join the proctodeum and to form the cloaca. Nphp4-deficient pronephric duct cells failed to connect with their ectodermal counterparts, and instead formed a vesicle at the obstructed end of the pronephric duct. Nephrocystin-4 interacts with nephrocystin-1 and Par6. Depletion of zebrafish NPHP1 (nphp1) increased the incidence of cyst formation and randomization of the normal body axis, but did not augment cloaca malformation in nphp4-deficient zebrafish embryos. However, simultaneous depletion of zebrafish Par6 (pard6) aggravated cloaca formation defects in nphp4-depleted embryos, suggesting that nphp4 orchestrates directed cell migration and cloaca formation through interaction with the Par protein complex.

Replication of 2 subtypes of low-pathogenicity avian influenza virus of duck and gull origins in experimentally infected Mallard ducks.

Many subtypes of low-pathogenicity avian influenza (LPAI) virus circulate in wild bird reservoirs, but their prevalence may vary among species. We aimed to compare by real-time reverse-transcriptase polymerase chain reaction, virus isolation, histology, and immunohistochemistry the distribution and pathogenicity of 2 such subtypes of markedly different origins in Mallard ducks (Anas platyrhynchos): H2N3 isolated from a Mallard duck and H13N6 isolated from a Ring-billed Gull (Larus delawarensis). Following intratracheal and intraesophageal inoculation, neither virus caused detectable clinical signs, although H2N3 virus infection was associated with a significantly decreased body weight gain during the period of virus shedding. Both viruses replicated in the lungs and air sacs until approximately day 3 after inoculation and were associated with a locally extensive interstitial, exudative, and proliferative pneumonia. Subtype H2N3, but not subtype H13N6, went on to infect the epithelia of the intestinal mucosa and cloacal bursa, where it replicated without causing lesions until approximately day 5 after inoculation. Larger quantities of subtype H2N3 virus were detected in cloacal swabs than in pharyngeal swabs. The possible clinical significance of LPAI virus-associated pulmonary lesions and intestinal tract infection in ducks deserves further evaluation.

Genital form of pasteurellosis in breeding turkeys infected during artificial insemination and isolation of an unusual strain of Pasteurella multocida.

A genital and potentially fatal form of Pasteurella multocida infection was reported on two turkey-breeding farms on which birds were vaccinated against Pasteurella multocida. Both outbreaks were linked to the use of semen from young vaccinated toms with a history of respiratory pasteurellosis followed by treatment during rearing. Typing by agar gel immunodiffusion and rapid slide agglutination of P. multocida isolated from cloacal swabs was completed by multilocus sequence typing. Restriction enzyme analysis showed that that the isolates were clonal. They belonged to sequence type (ST) 30, described in chickens, cats, and ducks. This strain differed in sequence type from the ones used in the vaccine (ST8, ST60, ST53, and ST235), which might have limited its effectiveness. No contamination of the semen (n = 30) was found, suggesting fecal contamination during semen collection.

Fetal MRI of cloacal exstrophy.

BACKGROUND: Prenatal ultrasonographic (US) diagnosis of cloacal exstrophy (CE) is challenging. OBJECTIVE: To define the fetal MRI findings in CE. MATERIALS AND METHODS: We performed a retrospective review of eight patients with CE. Imaging was performed between 22 weeks and 36 weeks of gestation with US in four and MRI in eight fetuses. Abdominal wall, gastrointestinal/genitourinary, and spine and limb abnormalities detected were compared with postnatal evaluation. RESULTS: US failed to display CE in one of the four fetuses. Fetal MRI confirmed CE in all eight fetuses by demonstrating absence of a normal bladder and lack of meconium-filled rectum/colon, associated with protuberant pelvic contour and omphalocele. These findings correlated postnatally with CE, atretic hindgut and omphalocele. One fetus had imaging before rupture of the cloacal membrane, showing a protruding pelvic cyst. Absent bladder was noted in the remaining seven fetuses. Confirmed skin-covered spinal defects were noted in seven fetuses, low conus/tethered cord in one and clubfoot in three. Six fetuses had renal anomalies, two had hydrocolpos and one had ambiguous genitalia. CONCLUSION: Fetal MRI provides a confident diagnosis of CE when a normal bladder is not identified, there is a protuberant abdominopelvic contour and there is absence of meconium-filled rectum and colon. Genitourinary and spinal malformations are common associations.

Congenital prepubic sinus associated with a urachal remnant: report of a case.

Congenital prepubic sinus is a rare congenital anomaly situated in the midline of the lower abdomen. We report a case of congenital prepubic sinus, closely associated with a urachal remnant. Preoperative magnetic resonance imaging showed clearly that the sinus tracked the urachus caudally. This finding supports the theory that the anomaly is caused by abnormal remnant tissue originating from the cloacal membrane, which tracks the allantois duct caudally along with fetal longitudinal growth.

Intestinal and cloacal strictures in free-ranging and aquarium-maintained green sea turtles (Chelonia mydas).

Intestinal or cloacal strictures that resulted in intestinal obstruction were diagnosed in six green sea turtles (Chelonia mydas) from three rehabilitation facilities and two zoologic parks. The etiologies of the strictures were unknown in these cases. It is likely that anatomic adaptations of the gastrointestinal tract unique to the green sea turtle's herbivorous diet, paired with causes of reduced intestinal motility, may predispose the species to intestinal damage and subsequent obstructive intestinal disease. In aquarium-maintained green sea turtles, obesity, diet, reduced physical activity, chronic intestinal disease, and inappropriate or inadequate antibiotics might also be potential contributing factors. Clinical, radiographic, and hematologic abnormalities common among most of these sea turtles include the following: positive buoyancy; lethargy; inappetence; regurgitation; obstipation; dilated bowel and accumulation of oral contrast material; anemia; hypoglycemia; hypoalbuminemia; hypocalcemia; and elevated creatine kinase, aspartate aminotransferase, and blood urea nitrogen. Although these abnormalities are nonspecific with many possible contributing factors, intestinal disease, including strictures, should be considered a differential in green sea turtles that demonstrate all or a combination of these clinical findings. Although diagnostic imaging, including radiographs, computed tomography, or magnetic resonance imaging, are important in determining a cause for suspected gastrointestinal disease and identifying an anatomic location of obstruction, intestinal strictures were not successfully identified when using these imaging modalities. Lower gastrointestinal contrast radiography, paired with the use of oral contrast, was useful in identifying the suspected site of intestinal obstruction in two cases. Colonoscopy was instrumental in visually diagnosing intestinal stricture in one case. Therefore, lower gastrointestinal contrast radiography and colonoscopy should be considered in green turtles when gastrointestinal obstructions are suspected. Although partial strictures of the cloacal opening may be identified on gross examination and might be managed with appropriate medical treatment, surgical intervention or humane euthanasia are likely the only options for sea turtles once small or large intestinal strictures have formed.