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VACTERL/VATER association is typically defined by the presence of at least three of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. In addition to these core component features, patients may also have other congenital anomalies. Although diagnostic criteria vary, the incidence is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The condition is ascertained clinically by the presence of the above-mentioned malformations; importantly, there should be no clinical or laboratory-based evidence for the presence of one of the many similar conditions, as the differential diagnosis is relatively large. This differential diagnosis includes (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus. Though there are hints regarding causation, the aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. New genetic research methods offer promise that the causes of VACTERL association will be better defined in the relatively near future. Antenatal diagnosis can be challenging, as certain component features can be difficult to ascertain prior to birth. The management of patients with VACTERL/VATER association typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment.

Background There is a wide spectrum of anorectal malformations (ARMs). The majority of ARM types can be diagnosed thorough perineal examination and radiological investigations such as MRI and distal loopogram. The most important aim of ARM repair is keeping the rectum in the muscle complex to protect continence, but still there are important factors that influence continence such as spine anomalies and associated urological anomalies. Case presentation In our report we describe two patients with ARM and abnormal anal sphincteric locations. The first case was a two-year-old female patient who presented with a massive perineal mass and peculiar female external genitalia that covers the entire perineum. Examination under general anaesthesia (EUA) revealed an extensive perineal lipoma that extends from the posterior point of the coccyx to the middle anterior separated pubic bone overlying a cavity separating it from a normal vaginal introitus containing normal urethral meatus, bicuspid Hymen and anorectal malformation with a vestibular fistula. MRI pelvis showed a large perineal lipoma. Surgical removal of the perineal mass, restoration of the perineal body and external genitalia, and anorectoplasty were performed. The second case was a 13-year-old male who is known to have bladder exstrophy but presented with mucosal bridges producing mucous and abnormally located anus. Excision of the mucosal bridge and confirming the accurate location of the anus within the muscle complex was performed. Conclusions It is important to look for and put into consideration other anomalies which can be associated with ARMs and influence the continence, in addition, to accurately locating the sphincter muscle complex using muscle stimulation to ensure placement of the anus within the complex to provide the best bowel function outcome for these cases.

Purpose Y-V anoplasty, traditionally performed for anal stenosis, was applied to treat patients with imperforate anus with recto-perineal fistula located at the anterior margin of the external anal sphincter, defined as Minimal Recto-Perineal Fistula(MRPF). We present our 20-year experience using this approach in patients with MRPF, with a minimum follow-up of 5 years. Methods This retrospective two-center study included patients who underwent Y-V anoplasty for MRPF between 2005 and 2020. The data collected included demographics, associated malformations, preoperative work-up, surgical details, postoperative management, complications, and long-term outcomes. Continence was evaluated using Rintala and Krickenbeck scores. Quality of life was assessed using the Incontinence-QoL score. Results Thirty-nine children (20 females) were included. Associated malformations were present in 23% of cases. Median age at surgery was 1.8 months. All patients underwent short-term anal dilatations. No early complications occurred. Median follow-up was 10.1 years. One patient was lost to follow-up. No cases of anal stenosis or prolapse were observed. Constipation was detected in 26% (10/38) of patients and was conservatively managed in all cases. Median scores were QoL 10/10, Krickenbeck 7/7 and Rintala 19.5/20. Conclusion Y-V anoplasty is a safe, reproducible, and sphincter-preserving technique. It is suitable for selected MRPF cases after careful anatomical assessment. Long-term functional and cosmetic outcomes are excellent.

Primary cilia are sensory organelles crucial for cell signaling during development and organ homeostasis. Cilia arise from centrosomes and their formation and function is governed by numerous factors. Through our studies on Townes-Brocks Syndrome (TBS), a rare disease linked to abnormal cilia formation in human fibroblasts, we uncovered the leucine-zipper protein LUZP1 as an interactor of truncated SALL1, a dominantly-acting protein causing the disease. Using TurboID proximity labeling and pulldowns, we show that LUZP1 associates with factors linked to centrosome and actin filaments. Here, we show that LUZP1 is a cilia regulator. It localizes around the centrioles and to actin cytoskeleton. Loss of LUZP1 reduces F-actin levels, facilitates ciliogenesis and alters Sonic Hedgehog signaling, pointing to a key role in cytoskeleton-cilia interdependency. Truncated SALL1 increases the ubiquitin proteasome-mediated degradation of LUZP1. Together with other factors, alterations in LUZP1 may be contributing to TBS etiology. Primary cilia are the ‘antennae’ of animal cells: these small, flexible protrusions emerge from the surface of cells, where they help to sense and relay external signals. Cilia are assembled with the help of the cytoskeleton, a dynamic network of mesh-like filaments that spans the interior of the cell and controls many different biological processes. If cilia do not work properly, human diseases called ciliopathies can emerge. Townes-Brocks Syndrome (TBS) is an incurable disease that presents a range of symptoms such as malformations of the toes or fingers, hearing impairment, and kidney or heart problems. It is caused by a change in the gene that codes for a protein called SALL1, and recent work has also showed that the cells of TBS patients have defective cilia. In addition, this prior research identified a second protein that interacted with the mutant version of SALL1; called LUZP1, this protein is already known to help maintain the cytoskeleton. In this study, Bozal-Basterra et al. wanted to find out if LUZP1 caused the cilia defects in TBS. First, the protein was removed from mouse cells grown in the laboratory, which dramatically weakened the cytoskeleton. In keeping with this observation, both the number of cilia per cell and the length of the cilia were abnormal. Cells lacking LUZP1 also had defects in a signalling process that transmits signals received by cilia to different parts of the cell. All these defects were previously observed in cells isolated from TBS patients. In addition, LUZP1-deficient mouse cells showed the same problems with their cilia and cytoskeleton as the cells from individuals with TBS. Crucially, the cells from human TBS patients also had much lower levels of LUZP1 than normal, suggesting that the protein may contribute to the cilia defects present in this disease. The work by Bozal-Basterra et al. sheds light on how primary cilia depend on the cytoskeleton, while also providing new insight into TBS. In the future, this knowledge could help researchers to develop therapies for this rare and currently untreatable disease.

This research aimed to assess the validity of ultrasound scans with new features in detecting fetal anal atresia and verify the effectiveness of these new features. Additionally, we aimed at investigating the perinatal incidence of anal atresia. This multicenter prospective study recruited 94,617 normal gravidas and 84 gravidas with anal atresia fetuses. The gold standard for diagnosing perinatal anal atresia is routine neonatal anus examinations. The incidence calculation was based on the results of the gold standard. The validity of our new approach was evaluated via a diagnostic test involving all 94,701 subjects. The effectiveness of our new features was assessed through an ablation study in a randomly established new dataset, with the ratio of anal atresia to non-anal atresia cases of 1:4. The annual perinatal incidence of anal atresia between 2019 and 2023 ranges from 0.57‰ to 1.29‰. Our new method performed great regarding the Youden index, diagnostic odds ratio (DOR), area under the curve (AUC) of the receiver operating characteristic curve (ROCC), AUC of the precision-recall curve (PRC), F1-score, and Cramer’s V. In the ablation study, our new approach surpassed its competitors concerning Youden index, DOR, AUC of the ROCC, and AUC of the PRC. Ultrasound scans show high validity and clinical value in detecting fetal anal atresia. Our new ultrasound features significantly promote the detection of fetal anal atresia.

The goal of surgery for anorectal malformations (ARM) is to achieve good bowel, urinary, and sexual functions, as well as the ability for children to become healthy adults. Various surgical procedures and surgical management protocols have been explored or devised by pediatric surgeons. These are described in this review. Making a correct type classification by invertography, fistelography and urethrography in the neonatal period allows pediatric surgeons to select an appropriate surgical strategy. Surgery for low-type malformations is principally neonatal perineoplasty, while that for intermediate- or high-type malformations is colostomy, followed by a pull-through operation during infancy. Posterior sagittal anorectoplasty or laparoscopy-assisted surgery has recently been accepted as alternative procedures. Fecal incontinence represents a devastating problem that often prevents a patient from becoming socially accepted and may cause serious psychological sequelae. One-third of adult patients with high- or intermediate-type malformations occasionally complain of fecal incontinence after surgery. Most patients with ARM have normal urinary function if they do not have urinary tract or sacral anomalies. These associated anomalies also influence the prognosis for sexual function, especially in males. Some female patients have experienced normal vaginal delivery and had children. In patients with cloacal malformation, however, fertility or sexual problems are also often present. Based on this information, it is clear that only well-planned and systemic treatments can provide a good functional prognosis after making a correct classification in the neonatal period.

Objective To compare MRI and colostography/fistulography in neonates with anorectal malformations (ARM), using surgery as reference standard. Methods Thirty-three neonates (22 boys) with ARM were included. All patients underwent both preoperative high-resolution MRI (without sedation or contrast instillation) and colostography/fistulography. The Krickenbeck classification was used to classify anorectal malformations, and the level of the rectal ending in relation to the levator muscle was evaluated. Results Subjects included nine patients with a bulbar recto-urethral fistula, six with a prostatic recto-urethral fistula, five with a vestibular fistula, five with a cloacal malformation, four without fistula, one with a H-type fistula, one with anal stenosis, one with a rectoperineal fistula and one with a bladderneck fistula. MRI and colostography/fistulography predicted anatomy in 88 % (29/33) and 61 % (20/33) of cases, respectively ( p  = 0.012). The distal end of the rectal pouch was correctly predicted in 88 % (29/33) and 67 % (22/33) of cases, respectively ( p  = 0.065). The length of the common channel in cloacal malformation was predicted with MRI in all (100 %, 5/5) and in 80 % of cases (4/5) with colostography/fistulography. Two bowel perforations occurred during colostography/fistulography. Conclusions MRI provides the most accurate evaluation of ARM and should be considered a serious alternative to colostography/fistulography during preoperative work-up. Key Points • High-resolution MRI is feasible without the use of sedation or anaesthesia . • MRI is more accurate than colostography/fistulography in visualising the type of ARM . • MRI is as reliable as colostography/fistulography in predicting the level of the rectal pouch . • Colostography/fistulography can be complicated by bowel perforation .

The ARM-Net (anorectal malformation network) consortium held a consensus meeting in which the classification of ARM and preoperative workup were evaluated with the aim of improving monitoring of treatment and outcome. The Krickenbeck classification of ARM and preoperative workup suggested by Levitt and Peña, used as a template, were discussed, and a collaborative consensus was achieved. The Krickenbeck classification is appropriate in describing ARM for clinical use. The preoperative workup was slightly modified. In males with a visible fistula, no cross-table lateral X-ray is needed and an anoplasty or (mini-) posterior sagittal anorectoplasty can directly be performed. In females with a small vestibular fistula (Hegar size <5 mm), a primary repair or colostomy is recommended; the repair may be delayed if the fistula admits a Hegar size >5 mm, and in the meantime, gentle painless dilatations can be performed. In both male and female perineal fistula and either a low birth weight (<2,000 g) or severe associated congenital anomalies, prolonged preoperative painless dilatations might be indicated to decrease perioperative morbidity caused by general anesthesia. The Krickenbeck classification is appropriate in describing ARM for clinical use. Some minor modifications to the preoperative workup by Levitt and Peña have been introduced in order to refine terminology and establish a comprehensive preoperative workup.

Background Anorectal malformations (ARM) are rare forms of congenital uro-rectal anomalies with largely unknown causes. Besides genetic factors, prenatal exposures of the parents to nicotine, alcohol, caffeine, illicit drugs, occupational hazards, overweight/obesity and diabetes mellitus are suspected as environmental risk factors. Methods Relevant studies published until August 2010 were identified through systematic search in PubMed, EMBASE, ISI Web of Knowledge and the Cochrane Library databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal and paternal smoking, maternal alcohol consumption, underweight (body mass index [BMI] < 18.5), overweight (BMI 25-29.9), obesity (BMI ≥30) and maternal diabetes mellitus with ARM using meta-analyses. Results 22 studies that reported on the association between prenatal environmental risk factors and infants born with ARM were included in this review. These were conducted in the United States of America (n = 12), Spain (n = 2), Sweden (n = 2), the Netherlands (n = 2), Japan (n = 1), France (n = 1), Germany (n = 1) and Hungary (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, control types and adjustment for covariates. Consistently increased risks were observed for paternal smoking and maternal overweight, obesity and diabetes, but not for maternal smoking and alcohol consumption. In meta-analyses, pooled odds ratios (95% confidence intervals) for paternal smoking, maternal overweight, obesity, pre-gestational and gestational diabetes were 1.53 (1.04-2.26), 1.25 (1.07-1.47), 1.64 (1.35-2.00), 4.51 (2.55-7.97) and 1.81 (1.23-2.65), respectively. Conclusion Evidence on risk factors for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate paternal smoking and maternal overweight, obesity and diabetes to be associated with increased risks. Further, ideally large-scale multicentre and register-based studies are needed to clarify the role of key risk factors for the development of ARM.

PurposeSurgical 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.MethodsAn 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).ResultsSixty-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).ConclusionDistinct fistula management strategies for PSARP and LAARP were revealed. Further studies are needed to investigate the postoperative outcomes associated with these practices.