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Purpose: Surgical procedures for anorectoplasty for anorectal malformations (ARMs), particularly rectourethral fistula (RUF), depend on the institution. We investigated the diagnosis and treatment of RUF in male patients with ARMs in Japan using a questionnaire survey., Methods: An online survey inquiring about the diagnosis and treatment (diagnostic modalities, surgical approaches, fistula dissection devices, and fistula closure techniques) of each type of ARM in male patients was conducted among institutional members of the Japanese Study Group of Anorectal Anomalies. Fisher's exact test was used to compare surgical methods between posterior sagittal anorectoplasty (PSARP) and laparoscopy-assisted anorectoplasty (LAARP)., Results: Sixty-one institutions (100%) completed the survey. LAARP was the preferred approach for high-type ARM (75.4%). PSARP was preferred for intermediate-type ARM (59.0%). Monopolar devices were most commonly used (72.1%) for RUF dissection. Blunt dissection was more frequent in the PSARP group (PSARP vs. LAARP: 55.6 vs. 20.0%, p < 0.005). Cystoscopy/urethroscopy to confirm the extent of dissection was used more frequently in the LAARP group (70.0% vs. 25.0%, p < 0.005). Clips and staplers were used more frequently in the LAARP group (p < 0.05)., Conclusion: Distinct fistula management strategies for PSARP and LAARP were revealed. Further studies are needed to investigate the postoperative outcomes associated with these practices., (© 2024. The Author(s).)

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function., (© 2024 Asian Pacific Society of Nephrology.)

Purpose: Congenital anorectal stenosis is managed by dilations or operative repair. Recent studies now propose use of dilations as the primary treatment modality to potentially defer or eliminate the need for surgical repair. We aim to characterize the management and outcomes of these patients via a multi-institutional review using the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) registry., Methods: A retrospective database review was performed using the PCPLC registry. The patients were evaluated for demographics, co-morbidities, diagnostic work-up, surgical intervention, current bowel management, and complications., Results: 64 patients with anal or rectal stenosis were identified (57 anal, 7 rectal) from a total of 14 hospital centers. 59.6% (anal) and 42.9% (rectal) were male. The median age was 3.2 (anal) and 1.9 years (rectal). 11 patients with anal stenosis also had Currarino Syndrome with 10 of the 11 patients diagnosed with a presacral mass compared to only one rectal stenosis with Currarino Syndrome and a presacral mass. 13 patients (22.8%, anal) and one (14.3%, rectal) underwent surgical correction. Nine patients (8 anal, 1 rectal) underwent PSARP. Other procedures performed were cutback anoplasty and anterior anorectoplasty. The median age at repair was 8.4 months (anal) and 10 days old (rectal). One patient had a wound complication in the anal stenosis group. Bowel management at last visit showed little differences between groups or treatment approach., Conclusion: The PCPLC registry demonstrated that these patients can often be managed successfully with dilations alone. PSARP is the most common surgical repair chosen for those who undergo surgical repair., Level of Evidence: III., Competing Interests: Conflict of interest Many authors are members of this consortium but have no financial or further competing interests in the outcomes of the study. All other authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study describes the presentation and initial management of anorectal malformation (ARM); evaluating the frequency, causes and consequences of late diagnosis., Methods: A prospective, population cohort study was undertaken for newly diagnosed ARMs in the UK and Ireland from 01/10/2015 and 30/09/2016. Follow-up was completed at one year. Data are presented as n (%), appropriate statistical methods used. Factors associated with late diagnosis; defined as: detection of ARM either following discharge or more than 72 h after birth were assessed with univariable logistic regression., Results: Twenty six centres reported on 174 cases, 158 of which were classified according to the type of malformation and 154 had completed surgical data. Overall, perineal fistula was the most commonly detected anomaly 43/158 (27%); of the 41 of these children undergoing surgery, 15 (37%) had a stoma formed. 21/154 (14%, CI 95 {9-20}) patients undergoing surgery experienced post-operative complications. Thirty-nine (22%) were diagnosed late and 12 (7%) were detected >30 days after birth. Factors associated with late diagnosis included female sex (OR 2.06; 1.0-4.26), having a visible perineal opening (OR 2.63; 1.21-5.67) and anomalies leading to visible meconium on the perineum (OR 18.74; 2.47-141.73). 56/174 (32%) had a diagnosis of VACTERL association (vertebral, anorectal, cardiac, tracheal, oesophageal, renal and limb); however, not all infants were investigated for commonly associated anomalies. 51/140 (36%) had a cardiac anomaly detected on echocardiogram., Conclusion: There is room for improvement within the care for infants born with ARM in the UK and Ireland. Upskilling those performing neonatal examination to allow timely diagnosis, instruction of universal screening for associated anomalies and further analysis of the factors leading to clinically unnecessary stoma formation are warranted., Level of Evidence: II (Prospective Cohort Study <80% follow-up)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Pentalogy of Fallot is a rare form of congenital cyanotic heart disease with a prevalence of 3/10,000 live births characterized by an association of Tetralogy of Fallot with Atrial Septal Defect. Pentalogy of Fallot with anorectal malformation is also a rare combination. Here we describe one of the rare case reports of a full-term, 38 weeks, female baby diagnosed with pentalogy of Fallot with imperforate anus and rectovaginal fistula at a tertiary care hospital. Pentalogy of Fallot combined with an imperforate anus and rectovaginal fistula is an exceptionally rare and complex congenital condition. The co- existence of these anomalies emphasizes the need for thorough prenatal and postnatal evaluation for early detection and management.

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., (© 2024 Wiley Periodicals LLC.)

Abstract: Genitourinary prolapse in newborn females as an introital mass is an uncommon entity. The usual causative mechanisms are poor pelvic innervation, damage or pressure on pelvic musculature and ligaments etc. Different methods of reduction as treatment were proposed in the past. Apart from uncommon occurrence of genitourinary prolapse in newborns, its association with anorectal malformation is not reported in English literature after searching on PubMed and Google Scholar. We report three cases of genitourinary prolapse with anorectal malformation in newborn females where decompressing colostomy was curative for the condition reflecting increased intra-abdominal pressure as causative mechanism., (Copyright © 2023 Copyright: © 2023 African Journal of Paediatric Surgery.)

Background: Anorectal malformations (ARMs) are congenital anomalies of the anorectum and the genitourinary system that result in a broad spectrum of hindgut anomalies. Despite surgical correction patients continue to have late postoperative genitourinary and colorectal dysfunction that have significant impact on quality of life., Aim: This paper will review the current evidence and discuss the evaluation and management of postoperative patients with ARMs who present with persistent defecation disorder., Methods: A literature search was conducted using PubMed/MEDLINE/EMBASE databases applying the following terms: ARMs, imperforate anus, constipation, faecal incontinence, neurogenic bowel, posterior sagittal anorectoplasty., Results: Patients who present with postoperative defecation disorders require timely diagnostic and surgical evaluation for anatomic abnormalities prior to initiation of bowel management. Goals of management are to avoid constipation in young children, achieve faecal continence in early childhood and facilitate independence in older children and adolescents. Treatment options vary from high dose stimulant laxatives to high-volume retrograde and antegrade enemas that facilitate mechanical colonic emptying., Conclusions: Appropriate diagnostic work-up and implementation of treatment can decrease long-term morbidity and improve quality of life in postoperative patients with ARMs who presents with defecation disorders., (© 2024 John Wiley & Sons Ltd.)

Abstract: Currarino syndrome (CS) is a rare congenital syndrome characterized by a triad of anorectal malformation, sacral deformity, and presacral mass. In about 50% of cases, it is caused by HLXB9 gene mutation in chromosome 7q36. A 13-month-male child presented with presacral discharging sinus with a history of surgery for anorectal malformation and perineal fistula at the time of birth. On detailed investigation, the child revealed to have anal atresia, hemisacrum, and presacral mass. Histopathology of presacral mass showed features of immature teratoma. The presacral mass in CS is mostly an anterior myelomeningocele or presacral teratoma. The development of immature teratoma in presacral mass is very rare. The histopathological identification of immature component of teratoma in the presacral mass of CS is important for risk stratification and further management. Suspicion of CS should be raised in any child presenting with partial phenotype of the triad., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Urorectal septum malformation sequence (URSMS) is an uncommon disease characterized by a failure of the anorectal septum to divide the cloaca and fuse with the cloacal membrane. Complete URSMS is usually lethal in newborn due to severe renal dysfunction and pulmonary hypoplasia. Partial URSMS is compatible with life with a single perineal opening draining a common cloaca with an imperforate anus which amenable to surgical management. Antenatal diagnosis of URSMS is challenging because of multisystem, complex abnormalities involving gastrointestinal, urogenital tract, cardiovascular, and musculoskeletal systems. In this case report, we describe a 15-week male fetus with partial URSMS having a spectrum of multisystem structural anomalies associated with fetal neuroblastoma in retroperitoneal location and adrenal neuroblastoma in situ., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

An 11-year-old girl with a history of imperforate anus, urinary tract infection, and intermittent episodes of constipation presented with abdominal pain and nausea for 1 week. The x-rays revealed hydrometrocolpos and fused pelvic kidney with a single hydronephrotic ureter. The vaginal examination revealed a nonpermeable transverse vaginal septum. The collection was temporarily drained and symptoms resolved. The patient was scheduled for definitive vaginal reconstructive surgery. In this case, it is worth noting the association of infrequent malformations and also the signs and symptoms very common in pediatric practice due to a pathology rarely considered in the differential diagnosis, and the importance of an early and complete assessment of this type of malformations for a timely treatment., (Sociedad Argentina de Pediatría.)

Omphalocele, exstrophy of cloaca, imperforate anus, and spinal defects complex is a rare malformation complex that includes omphalocele, cloacal exstrophy, imperforate anus and spinal defects with the incidence of 1 in 200,000 to 400,000 pregnancies and is even rarer in twin gestation. The etiology of this complex is still unclear. Most cases are sporadic. Prenatal screening must be done for diagnosis and appropriate multidisciplinary management of cases. In severe cases, termination of pregnancy is considered. We present a 4-day first twin child with underdeveloped ambiguous genitalia delivered via emergency lower section cesarean section at 32+3 weeks of gestation with giant liver containing omphalocele, cloacal exstrophy, imperforate anus and meningocele with severe pulmonary artery hypertension and non-visualization of right kidney and ureter, absence of uterus, fallopian tubes and right ovary. Separation and repair of the cecum and bladder were done. The ladd procedure was performed. Ileostomy was created and single-stage repair of the abdominal wall was done., Keywords: anorectal malformations; bladder exstrophy; case reports; neural tube defects; umbilicus.

Urorectal septum malformation sequence (URSMS) is characterized by a spectrum of anomalies of the urogenital system, hindgut and perineum. It is presumed to be a constellation of an embryonic defect. Herein, we analyzed the clinically diverse syndromes associated with URSMS in our perinatal evaluation unit. We reviewed fetuses with URSMS in referrals for perinatal autopsy over a period of 3 years. Chromosomal microarray and genome sequencing were performed whenever feasible. Literature was reviewed for syndromes or malformations with URSMS. We ascertained URSMS in 12 of the 215 (5%) fetuses. Nine fetuses (75%) had complete URSMS and remainder had partial/intermediate URSMS. Eleven fetuses had malformations of other systems that included: cerebral ventriculomegaly; right aortic arch with double outlet right ventricle; microcephaly with fetal akinesia deformation sequence; ventricular septal defect and radial ray anomaly; thoraco-abdominoschisis and limb defects; myelomeningocele; spina bifida and fused iliac bones; omphalocele; occipital encephalocele; lower limb amelia and cleft foot. We report on six fetuses with recurrent and five fetuses with unique malformations/patterns where URSMS is a component. Exome sequencing (one family) and genome sequencing (eight families) were performed and were nondiagnostic. Additionally, we review the literature for genetic basis of this condition. URMS is a clinically heterogeneous condition and is a component of several multiple malformation syndromes. We describe several unique and recurrent malformations associated with URSMS., (© 2022 Wiley Periodicals LLC.)

Anorectal malformations (ARM) in females are identified by abnormal location of the anal opening. Management is guided by clinical examination to find the number of perineal openings. Two openings in the perineum of a female may be seen in cases of imperforate anus without fistula, vaginal agenesis with vestibular fistula or imperforate anus with recto-vaginal fistula (RVF). We present a case series of ARM with RVF and discuss their diagnosis and management.

Objective: To explore the genetic basis for a child presented with renal failure and multi-cystic dysplastic kidney without anal atresia., Methods: Peripheral blood sample of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing., Results: The 40-day-old infant had presented with vomiting brown matter in a 7 days neonate and was transferred for kidney failure. Clinical examination has discovered renal failure, polycystic renal dysplasia, congenital hypothyroidism, bilateral thumb polydactyly, sensorineural hearing loss and preauricular dermatophyte. Genetic testing revealed that he has harbored a previously unreported c.824delT, p.L275Yfs*10 frameshift variant of SALL1 gene, which was confirmed by Sanger sequencing as de novo., Conclusion: The patient was diagnosed with Townes-Brocks syndrome due to the novel de novo variant of SALL1 gene. Townes-Brocks syndrome without anal atresia is rare. Above finding has also enriched the mutational spectrum of the SALL1 gene.

Rectal duplications are rare congenital anomalies that represent 1%-6% of alimentary tract duplications. We report a case of a woman in her 50s who presented to our hospital with perianal pain and urinary retention. She had a history of imperforate anus repaired after birth and dynamic graciloplasty performed during her adulthood for faecal incontinence. Abdominal CT scan showed a fluid collection extending from the electrostimulator, placed in a subcutaneous pocket in the abdomen, to the rectouterine pouch. Infection related to the electrostimulator was assumed and, after a course of antibiotics without patient improvement, the electrostimulator was removed. The symptoms and the pelvic fluid collection persisted, and diagnostic laparoscopy was performed. Diagnosis of rectal duplication cyst was made intraoperatively, and the cyst was completely resected. Patient fully recovered after surgery. This is a rare case of a rectal duplication cyst presenting during adulthood and associated with imperforate anus., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Townes-Brocks syndrome (TBS) is a rare autosomal dominant syndrome, resulting from heterozygous variant in SALL1 gene and initially characterized by the triad of anorectal, thumb, and ear malformations. Essentially described in children, adult case reports are uncommon. Renal involvement has already been reported in adults and children but poorly described. Structural abnormalities such as hypodysplasia, unilateral renal agenesis or multicystic kidneys have been described, as well as functional impairment (with or without structural abnormalities) that may progress to end-stage renal disease (ESRD). We report two adult cases (mother and daughter) which exhibited kidney hypoplasia (focal and segmental glomerulosclerosis for the mother) and ESRD. The mother had unilateral polydactyly. TBS was suggested after physical examination. TBS diagnosis was confirmed by identification of a SALL1 variant. We conducted a literature review to evaluate the renal anomalies in TBS cases diagnosed in adulthood. Among 44 adult cases of TBS with genetic confirmation (including our two cases), 10 had kidney disease. The circumstances of renal failure diagnosis were incidental findings (2/5), gout (2/5), or repeated episodes of pyelonephritis (1/5). The median age of kidney disease diagnosis was 30 years old and of renal transplant 49 years old. The most frequent renal malformation was bilateral kidney hypoplasia. TBS is probably underestimated in adulthood and this report highlights that less obvious elements of morphology such as dysplasic ears can facilitate the diagnosis of TBS. As long-term prognosis of renal involvement in TBS patients remains largely unknown, a regular evaluation is required throughout life for patients., (© 2021 Wiley Periodicals LLC.)

A challenge when repairing imperforate anus is positioning the neo-rectum into the center of the sphincter muscle complex (SMC) with limited muscle injury and scarring. Unfortunately, the path through the components of the SMC are often non-linear. We have used MRI to delineate the complex and guide the needle through the center using standard MRI-guidance (Raschbaum GR et al. J Pediatr Surg 45:220-223, 2010; Thomas TT et al. J Pediatr Surg 35:927-930, 2000). However, asynchronous scanning requires multiple, time-consuming scans to advance the needle in stepwise fashion. Asynchronous scanning also prevents visualizing the needle as it is advanced. We recently integrated software into the MRI operative suite that allows placement of the needle with real-time MRI. We report the feasibility and utility of real-time MRI-assisted laparoscopic assisted anorectoplasty (RT MRI-LAARP). Needle guidance was performed with Siemens Espree 1.5 T MRI with T1 Flash RT Sequence. After needle placement, laparoscopic mobilization, fistula takedown and pull-through was performed using the needle to guide dilation to create a tract to pull-through the neo-rectum. Charts of patients who underwent RT MRI-LAARP were reviewed. Demographics, anatomy, number of needle passes, OR duration and complications are reported. There were five children that underwent RT MRI-LAARP; one was a redo secondary to a retracted rectovestibular fistula. Operative time ranged from 187-505 min. Average hospital stay was 4.0 ± 1.0 days. There were no intraoperative complications although one patient had temporary urinary retention post-op. Muscle sparring laparoscopic anorectoplasty using real-time MRI is feasible and facilitates needle placement through the SMC.

Johanson-Blizzard Syndrome (JBS) is a rare autosomal recessive genetic disorder characterized by exocrine pancreatic insufficiency, distinct abnormal facial appearance and varying degrees of growth retardation. Variants in UBR1 gene are considered to be responsible for the syndrome. Here, we describe a 3-year old boy, who visited our clinic for severe growth retardation and frequent oily diarrhea. The physical examination revealed nasal alae aplasia, scalp defect, and maldescent of left testicle. Transabdominal ultrasound and computed tomography scan of his abdomen demonstrated complete fatty replacement of the pancreas. The clinical, laboratory, and imaging findings strongly suggest the diagnosis of hereditary pancreatitis. Whole exome sequencing revealed two rare compound heterozygous variants, c.2511T > G (p.H837Q) and c.1188T > G (p.Y396X), in the UBR1 gene of this boy, so, the diagnosis of JBS was established. This is the first report of Chinese patient with JBS, and our study indicates that transabdominal ultrasound and computed tomography are two useful and noninvasive imaging methods for the diagnosis and evaluation of JBS, and identification of these two novel variants expands the database of UBR1 gene variants. Furthermore, with the availability of the identification technology for these variants, prenatal diagnosis could be offered for future pregnancies., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10-year follow-up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow-up as well as adequate development and greater quality of life for patients with Down syndrome and their families., (© 2019 Wiley Periodicals, Inc.)

Background: The VATER/VACTERL association refers to the nonrandom co-occurrence of at least three of the following component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). Patients presenting with two CFs have been termed VATER/VACTERL-like phenotypes., Methods: We surveyed the exome for recessive disease variants in three affected sib-pairs. Sib-pair 971 consisted of two brothers with ARM and additional hydronephrosis in one brother. Sib-pair 1098 consisted of two sisters with ARM. In family 1346, the daughter presented with ARM and additional hypoplasia of both small fingers and ankyloses. Her brother presented with unilateral isolated radial hypoplasia. Sib-pairs 971 and 1346 resembled a VATER/VACTERL-like phenotype., Results: We detected a novel maternally inherited missense variant (c.1340G > T) and a rare paternally inherited deletion of the trans-allele in HSPA6 in both siblings of family 1346. HSPA6 belongs to the heat shock protein (HSP) 70 family. Re-sequencing of HSPA6 in 167 patients with VATER/VACTERL and VATER/VACTERL-like phenotypes did not reveal any additional bi-allelic variants., Conclusions: Until now, only TNF-receptor associated protein 1 (TRAP1) had been reported as an autosomal recessive disease-gene for the VATER/VACTERL association. TRAP1 belongs to the heat shock protein 90 family (HSP90). Both Hsp70 and Hsp90 genes have been shown to be important embryonic drivers in the formation of mouse embryonic forelimb tissue. Our results suggest HSPA6 as a new candidate gene in VATER/VACTERL-like phenotypes., (© 2019 Wiley Periodicals, Inc.)

Rationale: Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect (VACTERL) association and Müllerian duct anomalies are rare conditions. We present a rare condition with the co-occurrence of the VACTERL association and Müllerian duct hypoplasia to characterize patients' clinical presentations, outcomes, and treatment., Patient Concerns: An 11-year-old girl presented to our hospital with severe lower abdominal pain, lower vaginal atresia with enlargement of the upper vagina and a bicornuate uterus with a Y-shaped uterine cavity filled with hematometra on pelvic magnetic resonance imaging. Her medical history included congenital anal atresia with a rectovestibular fistula, congenital right renal deficiency, congenital right thumb malformation, and scoliosis., Diagnoses: 1. Congenital genital tract malformations, a partial bicornuate uterus, and distal vaginal atresia (U3aC0V4); 2. VACTERL association (congenital anal atresia with rectovestibular fistula, scoliosis with hemi vertebra and butterfly vertebra, unilateral renal agenesis, and finger defect)., Interventions: Colpotomy, laparoscopic exploration, pelvic adhesiolysis, and hysteroscopy were performed., Outcomes: Two months after surgery, a pelvic examination showed an unobstructed vagina which was 10 cm long and 2 fingers wide, without adhesion or constriction., Lessons: Clinicians should have a high index of suspicion when evaluating patients with genital malformations associated with VACTERL. Early diagnosis of distal vaginal atresia with appropriate surgical intervention decreases long-term morbidity.

We present a case of a child with pancreatic insufficiency and facial defects typical of Johanson-Blizzard syndrome (JBS), along with the more facultative anomalies of the JBS, such as those of the urogenital system including persistent urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth revealed a phallic structure with urethral meatus, non-palpable gonads, two orifices in close proximity in the perineum, with the anterior being a common urogenital channel and the posterior, the rectum. A voiding cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and a common urogenital sinus extending 1.5 cm before dividing into three channels: the native urethra, an accessory urethra directed anteriorly towards the clitoris and a septate vagina with uterus didelphys. JBS was suspected by clinical presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Johanson-Blizzard Syndrome (JBS) was first described by Johanson and Blizzard. It exhibits autosomal recessive inheritance and is characterized by mutation in the UBR1 gene on the long arm of Chromosome 15. The phenotypic features as well as diarrhoea that occurs due to the exocrine pancreatic insufficiency constitute the main clinical symptoms. This article discusses Johanson-Blizzard Syndrome due to the case followed-up by us with the symptoms of deafness and diarrhoea as well as typical facial appearance.

We here report the case of a male newborn admitted immediately after birth with imperforate anus. Physical examination of the anal margin showed imperforate anus; the examination of the external genitalia objectified scrotal bifidity with a fistula filled with meconium at the level of the penis root. During urinary catheterization the catheter passed through the fistula (A), suggesting a rare anorectal malformation with recto-uretrobulbar fistula. Malformation assessment was without abnormalities. The newborn was admitted to the operating room and clouding was performed during surgery by catheterization of the fistula using two 6 CH (1.98mm) Foley catheters, one passing through the rectum and the other passing through the bladder; a third foley catheter passed through the urethral meatus, objectifying the communication among the three catheters at the level of the recto-uretrobulbar fistula (B). The diagnosis of rare intermediate anorectal malformation was retained and colostomy was performed. The newborn underwent treatment based on perineal anorectoplasty with fistula closure at the age of 3 months. Anal dilatation was performed for 6 months. Colostomy closure was performed at the age of 9 months. Patient's evolution was favorable at 2-year follow-up.

Background: Townes-Brocks syndrome (TBS) is a rare autosomal dominant condition characterized by renal, anal, limb, and auditory abnormalities. TBS diagnosis can be challenging in settings where genetic analysis is not readily available. TBS traits overlap with those of Goldenhar and VACTERL syndromes., Case Presentation: Here, we present the case of a 5-year-old Brazilian boy born with an anorectal abnormality, limb and external ears malformations, genitourinary anomalies, and a congenital heart defect. Genetic analysis revealed a SALL1 nonsense mutation. The case is discussed in the context of the current literature., Conclusions: Because of the variability in TBS clinical presentation, genetic analysis is key to the differential diagnosis of TBS relative to phenotypically similar syndromes.

Cloacal exstrophy (CE) and persistent cloaca (PC) (alternatively termed urorectal septum malformation sequence [URSMS]), represent two major cloacal defects (CDs). Clinical characteristics and risk factors often are studied for both defects combined, rather than exploring if these defects have different etiologies. We enumerated clinical features for 47 CE and 54 PC (inclusive of URSMS) cases from the National Birth Defects Prevention Study. Thirty-three CE cases were classified as isolated and 14 as multiple (presence of unassociated major defects); respective totals for PC cases were 26 and 28. We compared selected child and maternal characteristics between 11,829 non-malformed controls and CE and PC cases using chi-square or Fisher's exact tests. Compared to controls, CE and PC cases were statistically more likely (p < 0.05) to be preterm; CE cases were more likely to be multiple births. We conducted logistic regression analysis to estimate odds ratios and 95% confidence intervals for any CD, CE, and PC with selected self-reported maternal prepregnancy and periconceptional (one month prior to 3 months following conception) exposures. In crude and adjusted analyses, we observed significant positive associations for any CD, CE, and PC with use of any fertility medication or assisted reproductive technology procedure. Significant positive associations observed only in crude analyses were any CD with maternal obesity or use of progesterone, any CD and CE with any x-ray, and any CD and PC with use of folate antagonist medications. Our findings provide some of the first insights into potential differing etiologies for CE and PC., (© 2017 Wiley Periodicals, Inc.)

Background: Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pathway., Methods: Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1 mutation on either one or both alleles were included in this study. In order to discover mutations that are not detectable by Sanger sequencing, we designed a probe set for multiplex ligation-dependent probe amplification (MLPA) analysis of the UBR1 gene and analyzed the copy number status of all 47 UBR1 exons., Results: Our previous studies using Sanger sequencing could detect mutations in 93.1% of 130 disease-associated UBR1 alleles. Six patients with a highly suggestive clinical diagnosis of JBS and unsolved genotype were included in this study. MLPA analysis detected six alleles harboring exon deletions/duplications, thereby raising the mutation detection rate in the entire cohort to 97.7% (127/130 alleles)., Conclusion: We conclude that single or multi-exon deletions or duplications account for a substantial proportion of JBS-associated UBR1 mutations., (© 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Mutations in CASK cause X-linked intellectual disability, microcephaly with pontine and cerebellar hypoplasia, optic atrophy, nystagmus, feeding difficulties, GI hypomotility, and seizures. Here we present a patient with a de novo carboxyl-terminus splice site mutation in CASK (c.2521-2A>G) and clinical features of the rare FG syndrome-4 (FGS4). We provide further characterization of genotype-phenotype correlations in CASK mutations and the presentation of nystagmus and the FGS4 phenotype. There is considerable variability in clinical phenotype among patients with a CASK mutation, even among variants predicted to have similar functionality. Our patient presented with developmental delay, nystagmus, and severe gastrointestinal and gastroesophageal complications. From a cognitive and neuropsychological perspective, language skills and IQ are within normal range, although visual-motor, motor development, behavior, and working memory were impaired. The c.2521-2A>G splice mutation leads to skipping of exon 26 and a 9 base-pair deletion associated with a cryptic splice site, leading to a 28-AA and a 3-AA in-frame deletion, respectively (p.Ala841&#95;Lys843del and p.Ala841&#95;Glu868del). The predominant mutant transcripts contain an aberrant guanylate kinase domain and thus are predicted to degrade CASK's ability to interact with important neuronal and ocular development proteins, including FRMD7. Upregulation of CASK as well as dysregulation among a number of interactors is also evident by RNA-seq. This is the second CASK mutation known to us as cause of FGS4. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Purpose: Surgical procedures for high imperforate anus have ranged from the posterior sagittal anorectoplasty (PSARP) to laparoscopic-assisted anorectoplasty (LAARP). PSARP bisects the sphincter muscle complex, introducing muscle injury and scarring. LAARP uses a straight trocar to traverse an often non-linear sphincter muscle complex. MRI-assisted LAARP (MRI-LAARP) guides the neorectum precisely through the middle of the entire sphincter complex along its trajectory. We present our experience utilizing MRI intraoperatively during LAARP., Methods/procedure: Ten children underwent MRI-LAARP procedures. Intraoperative MRI was performed to delineate the sphincter complex, and to guide the advancement of an MRI-compatible needle through the center of the complex from skin to the peritoneal cavity. The remainder of the procedure was completed using the standard LAARP technique., Results: All had successful MRI needle placement through the sphincter complex. Nine patients had successful laparoscopic pull-through procedures; one was converted to open due to severe intraperitoneal adhesions. Postoperative stay averaged 5.4 ± 4.4 days. Out of the ten patients, one child had mild dehiscence of the anal anastomosis requiring revision 11 days postoperatively., Conclusion: The theoretical advantage of the MRI-LAARP is placing the neorectum through the entire sphincter complex without transecting the muscle. Follow-up of these patients shows good short-term results; however, long-term follow-up will be needed to best assess sphincter and bowel function.

Johanson-Blizzard syndrome (JBS) is considered as an infrequent, but clinically easily recognizable autosomal recessive entity by the pathognomonic combination of congenital exocrine pancreatic insufficiency and hypoplastic alae nasi, in addition to other distinctive findings such as scalp defects, hypothyroidism, and rectourogenital malformations. There are few reports of patients with JBS in association with facial clefting, referring all to types 2 to 6 of Tessier's classification that can be characterized properly as oblique facial clefts (OFCs). We describe the clinical aspects in four patients with JBS and extensive OFCs. In all of them, the diagnosis of JBS was confirmed by the demonstration of homozygous or compound-heterozygous mutations in the UBR1 gene. Additionally, we review three previously reported cases of JBS with OFCs. Taking into account a number of approximately 100 individuals affected by JBS that have been published in the literature we estimate that the frequency of OFCs in JBS is between 5% and 10%. This report emphasizes that extensive OFCs may be the severe end of the spectrum of facial malformations occurring in JBS. No obvious genotype phenotype correlation could be identified within this cohort. Thus, UBR1 should be included within the list of contributory genes of OFCs, although the exact mechanism remains unknown. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Although anorectal malformations (ARMs) are frequently encountered, rare variants difficult to classify have been reported., Methods: This study describes a patient with ARM and rectopenile fistula. The literature was reviewed systematically to assess the anatomical characteristics, clinical presentations and operations of this rare type of ARM., Results: Eight patients were reported in the six included articles. In three patients, the fistula extended from the rectum to the anterior urethra without communication with the skin. In one patient, the fistula, located deep in corpus spongiosum, opened to the ventral aspect of the penis without communication with the urethra. In the remaining four patients, the fistula extended from the rectum to the cutaneous orifice in the ventral aspect of penis, with communication or a short common channel with the urethra., Conclusions: Imperforate anus with fistula extending into the penis is a rare variant of anorectal malformation. Unawareness of this lesion resulted in a delay of correct diagnosis and appropriate management. A thorough examination, including colonourethrography and fistulography, should be performed in all patients with a fistula opening in the ventral aspect of the penis.

Background: Straining at stool is an automatic reflex in babies and implies the presence of rectal sensation. We hypothesised that early reported rectal sensation would predict future continence in children with anorectal anomalies., Aim of the Study: The aim of this study is to determine if early straining at stool was a useful predictor of future continence in infants born with high anorectal malformations., Methods: A retrospective case note review of prospectively collected clinical information was performed with institutional review board approval. All patients with intermediate/high anorectal malformation operated on by a single surgeon from 1984 to 2010 were included. After stoma closure, parents were asked: The responses were noted within the first year of stoma closure and then all patients were followed up until they were at least 3 ½years old and continence could be assessed using the Krickenbeck outcome classification. Data were compared using Fisher's exact test and sensitivity, specificity and positive predictive value (PPV) were calculated., Main Results: Forty-eight patients were included in the study. Sixteen (33%) were female (12 cloacal malformation, 3 rectovaginal fistula, 1 rectal atresia) and 32 (66%) were male (6 rectovesical fistulae, 22 rectourethral fistulae, 4 no fistula). Median follow-up was 9.7years (range 3.5-17.9). Twenty-one children were noted by their parents to exhibit early straining at stool after stoma closure. Twenty of them achieved long term continence. The sensitivity of early straining as a predictor for long term continence was 77%, specificity 95% and positive predictive value 95%., Conclusion: The presence of early rectal sensation reported by parents is a good predictor of long term continence. This allows more informed discussion with families in the early years of life., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In 1981, Casamassima and colleagues described an autosomal recessive syndrome of spondylocostal dysostosis associated with anal and urogenital anomalies. Here, I describe 1 new fetus who presented with limb-body wall defect as a novel association, compile 7 patients, and review the clinical phenotype of Casamassima-Morton-Nance syndrome. This appears to be the 1st Casamassima-Morton-Nance syndrome fetus with this complex malformation. In light of this manifestation, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with significant clinical variability. Accordingly, it is proposed that Casamassima-Morton-Nance syndrome should be considered in those patients with the combination of a short and asymmetric thorax with rib and vertebral anomalies and scoliosis (spondylocostal-like pattern), anal atresia, absent external genitalia, renal and urethral abnormalities (caudal dysgenesis complex), craniofacial dysmorphic features (mainly flat nose with anteverted nares, low-set/abnormal ears, and short neck), hydrops, oligohydramnios, and a poor clinical outcome.

Polydactyly is among comnion extremity abnormalities. Mutations of GLI3 gene have been reported commonly in Greig Cephalopolysyndactyly Syndrome (GCPS) and Pallister-Hall Syndrome (PHS). We have determined two different mutations of GLI3 gene in two different cases, one of which is with GCPS and the other one is with PHS. A deletion mutation was detected in the proband with GCPS and his mother. Otherwise, we found that, unlike the previously reported, the mutation c.2437C>T, p.Q813X which was detected in the GLI3 gene caused typical PHS. We are in thought of that our cases will contribute to understanding of phenotypic variability leading to GLI3 mutations.

The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease-associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease-causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL., (© 2015 WILEY PERIODICALS, INC.)

Anorectal malformations (ARM) have a low prevalence, patients need specialized surgical care, and in many cases, patients born with ARM even need life-long aftercare. Due to its low prevalence most patients are still treated in low-volume pediatric surgical centers without any adequate monitoring of the outcome. Data on prevalence, comparison of different surgical techniques, and prospective outcome measurements are still scarce and difficult to interpret. In 2010, a consortium was founded (ARM-Net consortium) including several European pediatric surgical centers to collaborate more in research and share knowledge on ARM. One of the structures started by the consortium was an ARM-Net registry for the inclusion of all future patients treated in these centers. With this review, we report the structure of the ARM-Net registry, some of the results, and discuss the challenges we faced and still face after its introduction in 2010., (Georg Thieme Verlag KG Stuttgart · New York.)

OEIS complex is a rare entity comprising a combination of omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. We present a case that demonstrates the imaging features of OEIS complex, which also has the rare diagnosis of a terminal myelocystocele, across multiple imaging modalities both prenatally and postnatally. A prenatal diagnosis of OEIS complex allowed for appropriate planned multidisciplinary management of this patient., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The article provides the analysis of a survey of the professional community of Russian pediatric surgeons, dedicated to the treatment of anorectal malformations (ARM). The authors evaluated the differences and similarities in classification, surgical procedures, time of definitive repair, and postoperative management of ARM in different hospitals and centers. This was done by a survey upon specialists and experts in Russia followed by a symposium with live surgery, open discussion, and vote. Overall, 85% of the delegates supported the idea to create several regional centers of pediatric coloproctology as the way to improve the treatment of ARM in Russia. Moreover, 80% of delegates agreed to create a universal database of ARM information. The development of neonatal surgery and videoendoscopic surgical methods in the treatment of patients with ARM requires creation of a national guideline by the Russian Association of Pediatric Surgeons. Next step will concern standardization of the diagnosis and surgical treatment of children with ARM. This study is a collaborative effort to provide Russian Consensus on treatment of ARM., (Georg Thieme Verlag KG Stuttgart · New York.)