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Contains fulltext : 248942.pdf (Publisher’s version ) (Open Access) The caudal type homeobox 2 (CDX2) gene encodes a developmental regulator involved in caudal body patterning. Only three pathogenic variants in human CDX2 have been described, in patients with persistent cloaca, sirenomelia and/or renal and anogenital malformations. We identified five patients with de novo or inherited pathogenic variants in CDX2 with clinical phenotypes that partially overlap with previous cases, that is, imperforate anus and renal, urogenital and limb abnormalities. However, additional clinical features were seen including vertebral agenesis and we describe considerable phenotypic variability, even in unrelated patients with the same recurrent p.(Arg237His) variant. We propose CDX2 variants as rare genetic cause for a multiple congenital anomaly syndrome that can include features of caudal regression syndrome and VACTERL. A causative role is further substantiated by the relationship between CDX2 and other proteins encoded by genes that were previously linked to caudal abnormalities in humans, for example, TBXT (sacral agenesis and other vertebral segmentation defects) and CDX1 (anorectal malformations). Our findings confirm the essential role of CDX2 in caudal morphogenesis and formation of cloacal derivatives in humans, which to date has only been well characterized in animals.

Mermaid syndrome or sirenomelia is an extremely rare congenital malformation with an incidence between 1.5 and 4.2 per 1,000,000 pregnancies. Association of mermaid syndrome with VACTERL-H syndrome is extremely rare, with only two cases reported so far in the literature. We present a new case of type I sirenomelia associated with VACTERL-H syndrome and review the relevant literature. A 15-year-old female patient was admitted to the Department of Pathological Pregnancy at St George University Hospital, Plovdiv with progredient abortion during her first pregnancy. She had low socioeconomic status, negative history of concomitant diseases and addictions. The patient avoided prophylactic intake of folic acid during her pregnancy. Prenatal ultrasound found a malformative fetus. Consequently, magnetic resonance imaging was performed which established the presence of hydrocephalus and defects in the lower part of the spine. These pathological findings indicated interruption of pregnancy at 20 weeks of gestation. The fetopathological examination found sirenomelia type I associated with myelomeningocele, hydrocephalus, anal imperforation, single umbilical artery, bilateral renal and ureteric agenesis, bladder agenesis, tracheo-esophageal fistula, agenesis of external genitals, monkey fold of the left palm of the hand, also known as VACTERL-H syndrome. Our case demonstrates that mermaid syndrome and VACTERL-H syndrome represent different manifestations of a single pathological process that results in disorders of the blastogenesis at different stages during embryonic development.&nbsp

Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G>C on OLR1 and c.-8C>G on PSMA6 were previously associated with myocardial infarction. The variants c.1936A>G on AKAP10 and c.575A>G on PON1 are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G>A on EPHX2 and c.214C>A on GHRL. In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.

Horseshoe kidney is one of the most common congenital urologic anomalies, with an incidence of 1 in 400 live births. The presence of this type of fusion anomaly of kidneys with resultant progression to renal pathology sometimes may remain obscured or dormant, due to the person being asymptomatic for years, only to be incidentally encountered during an autopsy, or during a cadaveric dissection. Similarly, during routine cadaveric dissection, we came across with a list of variations along with congenital anomalous horseshoe kidney. In this case report, we discuss about anatomical variation and pathological findings of horseshoe kidney.

Rhombencephalosynapsis is a rare defect in the development of the cerebellum, characterized by partial or total agenesis of the vermis, with fusion of the cerebellar hemispheres in the midline. It is usually related to Gómez-López-Hernández Syndrome (cerebellar-trigeminal dermal dysplasia) and VACTERL association association (vertebral defects, vascular anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, renal dysplasia and limb anomalies). A 5-year-old female patient with spastic cerebral palsy and hydrocephalus presented here, neuroimages documented the next features: absence of cerebellar vermis, periventricular leukomalacia, cerebellar tonsils descent and rhombencephalosynapsis. Other important imaging findings and associations in these cases are discussed.

Introduction. Esophageal atresia (EA), typically occurring with tracheoesophageal fistula (TEF), is one of the most common digestive malformations; 50% of the esophageal atresia cases associate other malformations, syndromes or association of congenital abnormalities. EA is also met in patients with Edwards syndrome, Down syndrome, Di George syndrome and Pierre Robin syndrome. Delayed diagnosis of EA associated anomalies leads to increased morbidity and mortality, especially in patients with two or more associated abnormalities. Our study aims to highlight EA associated anomalies and to evaluate their impact on mortality. Materials and methods. We conducted a retrospective study of all newborns admitted in the Neonatal Intensive Care Unit of “Grigore Alexandrescu” Emergency Clinical Hospital for Children, with the diagnosis of esophageal atresia/ tracheoesophageal fistula (TEF), between January 2013 and December 2018; we evaluated demographic information, clinical manifestation, the ultrasound and radiological results. Our study aimed to highlight AE associated anomalies and to evaluate their impact on mortality. Results. 56 newborns with esophageal atresia/ tracheoesophageal fistula diagnosis were identified. 31 of them were boys, and 22 patients had gestational age (GA) between 32 and 36 weeks. Five newborns came from twin pregnancies. EA/ TEF associated anomalies were identified in 35 patients; the most frequent of those were cardiac anomalies (identified in 25 patients). The association of 3 anomalies from VACTERL spectrum (vertebral, anorectal, cardiac, EA/ TEF, renal and urinary, and limb lesions) was seen in 11 newborns. The estimated risk of death was lightly increased in females and in patients from urban area; the patients with limb anomalies had an estimated risk of death 5 times higher (p = 0.043). Conclusions. EA is a complex pathology both by the malformations and genetic syndromes that can be associated with it, and by the complications that occur in evolution. Antenatal diagnosis of EA and of the associated anomalies, along with multidisciplinary care, represent important measures in order to avoid underdiagnosis of associated problems.

Background The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. Methods A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. Results In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. Conclusion The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Introduction: Scoliosis is a well-described complication of esophageal atresia (EA) caused by the associated spine malformations and/or thoracotomy. However, the sagittal posture abnormalities in patients with EA have not been described. The aim of this study was to evaluate the prevalence of and risk factors for sagittal posture abnormalities at the age of 6 years in patients operated on for EA.Methods: A prospective cohort of 123 patients with EA was examined by the same rehabilitation doctor at the time of a multidisciplinary visit scheduled at the age of 6 years. Children presenting with scoliosis (n = 4) or who missed the consultation (n = 33) were excluded. Univariate and multivariate logistic regression models with Firth's penalized-likelihood approach were used to identify risk factors associated with sagittal posture anomalies. Candidate risk factors included neonatal characteristics, associated malformations, atresia type, postoperative complications, psychomotor development retardation, orthopedic abnormalities, and neurological hypotonia.Results: The prevalence rates of sagittal posture abnormalities were 25.6% (n = 22; 95% CI, 16.7–36.1%). Multivariate analysis showed that minor orthopedic abnormalities (OR: 4.02, 95% CI: 1.29–13.43, P = 0.021), and VACTERL (OR: 3.35, 95% CI: 1.09–10.71, P = 0.042) were significant risk factors for sagittal posture abnormalities.Conclusion: This study shows that sagittal posture anomalies occur frequently in children operated on at birth for EA and are not directly linked to the surgical repair. These children should be screened and treated using postural physiotherapy, especially those with VACTERL and minor orthopedic abnormalities.

Background:Assisted reproductive technologies (ART) are becoming widespread, accounting for approximately 2% of all births in the western countries. Concerns exist on the potential association of ART with congenital anomalies. Few studies have addressed if a relationship exists between ART and the development of anorectal malformation (ARM). Our aim was to analyze the relationship between ARM and ART.Methods:Single-center retrospective case control study of all patients treated for ARM between 2010 and 2017. Patients with bronchiolitis treated since 2014 were used as controls. Variables analyzed include the following: prevalence of ART, gestational age, birth weight, and maternal age. Patients with ARM born after ART were also compared with those naturally conceived for disease complexity. Fisher's exact and Mann-WhitneyU-tests were used as appropriate.Results:Three hundred sixty-nine patients were analyzed (143 cases and 226 controls). Prevalence of ART was significantly higher in ARM patients than in controls [7.6 vs. 3.0%; odds ratio: 2.59 (95% CI, 0.98–0.68);p= 0.05]. Among ARM patients, incidence of VACTERL association (17%) is more frequent in ART babies.Conclusion:Patients with ARM were more likely to be conceived following ART as compared with controls without congenital anomalies. Disease complexity of patients with ARM born after ART seems greater that those born after nonassisted conception.

Anorectal malformations (ARMs) can occur in isolation or in association with other anomalies, most commonly those of the genitourinary systems. Morbidity and mortality are highest among patients who develop end-stage renal disease (ESRD) either from severe congenital anomalies (dysplastic kidneys) or from repeated infections in those who have vesicoureteral reflux or persistent recto-urinary fistulas. We describe our management strategy for a patient born with an ARM and bilateral dysplastic kidneys to highlight the nuances and complex decision-making considerations required in taking care of this complex patient population. Our patient is a male twin born at 32 weeks’ gestational age who was found to have bilateral dysplastic kidneys on prenatal ultrasound. On initial examination, an imperforate anus was identified along with a severe urethral stricture. Full workup also revealed sacral dysgenesis and confirmation of the dysplastic kidneys. On day of life 3, a laparoscopic diverting sigmoid colostomy was performed; urologic evaluation confirmed the severe urethral stricture, which required dilation to place an 8F council tip catheter. Due to his small size, peritoneal dialysis could not be initiated until five weeks of age. As full volumes could not be reached with peritoneal dialysis, he was soon transitioned to continuous renal replacement therapy. At five months of age, a laparoscopic-assisted posterior sagittal anorectoplasty (PSARP) was performed. As his urethral stricture had worsened, a suprapubic catheter had been placed for bladder decompression. Reversal of his colostomy was performed 15 days after PSARP. Unfortunately, the patient required three further surgical interventions due to abdominal wall and inguinal hernias contributing to filling and emptying dysfunction when utilizing peritoneal dialysis. He is currently 16 months of age and remains inpatient due to intermittent hemodialysis requirements along with autocycling of his peritoneal dialysis. He is working on developmental milestones, can pull to a stand, and is currently being evaluated for kidney transplantation. The development of ESRD in a neonate or infant with an ARM is rare and can be due to congenital dysplasia or agenesis of bilateral kidneys. While peritoneal dialysis is the preferred approach, catheter dysfunction can result from intra-abdominal adhesions or inadequate fluid removal from inguinal or abdominal wall hernias that form in the setting of increased intra-abdominal pressure required for peritoneal dialysis. Close collaboration is required between pediatric surgeons, nephrologists, and urologists to facilitate colonic and urologic reconstruction and manage catheter-related complications.

VACTERL is a condition that includes various anatomic anomalies including vertebral, cardiac, tracheoesophageal fistula (TEF), renal, and limb defects. TEF can be found in up to 80% of patients with the condition. Although TEFs are usually identified early in life, the H-type TEF can be more difficult to detect. We report the case of a 15-year-old male with a previous diagnosis of VACTERL who presented with a history of recurrent pneumonia, chest pain, and asthma and was found to have a previously undetected H-type TEF that was surgically repaired. When evaluating a patient with features of VACTERL, it is important to choose studies that can explore the presence of all associated features. Clinical history and type of imaging utilized can be essential in making a timely diagnosis, especially for H-type TEF.

Introduction To our knowledge, there are no studies to date that have compared patients with isolated anorectal malformation (ARM) to patients with ARM and an associated genitourinary (GU) malformation despite a possible etiological difference between these two entities. We examined the differences in maternal and prenatal exposures and comorbidities between patients with isolated ARM and patients with ARM and associated GU malformations. Materials and methods A retrospective cohort study of children with ARM, enrolled in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) between February 2017 and October 2019, was performed comparing those with isolated ARM to those with ARM and associated GU anomalies (GU +/- additional anomalies) as well as to those with ARM and a GU anomaly with no anomaly of any other system (GU-only). We compared the prevalence of prematurity, family history of colorectal disorders, as well as maternal and prenatal comorbidities and exposures between these two cohorts and the isolated ARM cohort. Results A total of 505 patients (117 with isolated ARM and 388 with ARM and associated GU anomalies) were enrolled. Of the 388 patients with ARM and associated GU anomalies, 48 had an ARM with a GU anomaly without an anomaly in any other system. There was an increased prevalence of premature births in the GU +/- additional anomalies cohort compared to the isolated ARM cohort (27 vs 14%, p=0.003). This difference was not seen in the GU-only cohort. There was no difference between the cohorts regarding prevalence of family history of ARM or maternal and prenatal comorbidities or exposures. Conclusions Patients with an ARM and an associated GU anomaly with or without other congenital anomalies are more likely to be born prematurely compared to patients with an isolated ARM. Parents of these children should be counseled on this increased risk.

Highlights • High anorectal malformations (ARM) are associated with rectourinary fistulae. • Augmented-pressure colostogram is the gold standard in diagnosing recto-urinary fistulae in cases of ARM. • Cystoscopic assisted air colostogram can be used as an adjunctive diagnostic to augmented-pressure colostogram., Introduction Anorectal malformations (ARM) in newborns classically present with the absence of a normal anus or an abnormally located anus. In a male infant with a high ARM, an initial diverting colostomy is later followed by a definitive posterior sagittal anorectoplasty (PSARP). Prior to definitive surgery an augmented-pressure colostogram is performed to identify the location of the fistula between the rectum and urogenital tract. However, on occasion, the augmented-pressure colostogram fails to identify the location of the fistula tract. We present a case of ARM where augmented-pressure colostogram failed to identify a fistula tract, thus requiring an alternative diagnostic approach. Presentation of case A newborn male presented with a high anorectal malformation and suspected rectourinary fistula on initial augmented-pressure colostogram. The patient ultimately underwent a laparoscopic assisted PSARP after cystoscopy with air colostogram identified the exact location of the fistulous connection in the prostatic urethra. Discussion Augmented-pressure colostogram remains the gold standard in diagnosing rectourinary fistulae in cases of ARM. However, a number of alternative and adjunctive techniques have been proposed in recent years. We provide a brief review of the literature in addition to a case presentation highlighting the potential benefits of pre-operative cystoscopy-assisted air colostogram in male patients with ARM. Conclusion Cystoscopy-assisted air colostogram via a distal mucous fistula can be utilized as an alternative diagnostic modality, especially when the augmented-pressure distal colostogram fails to identify rectourinary fistulae in high anorectal malformations.

We report a rare case of a neonatal girl who presented with coughing and dyspnea immediately after feeds. At birth, she was noted to have an imperforate anus with a posterior fourchette fistula from which she was stooling. Initial imaging with radiography showed a normal bowel gas pattern; however, lumbar vertebral anomalies were noted. An upper GI series was performed and revealed a laryngeal cleft and malrotation. Ultrasound confirmed malrotation with an abnormal SMA-SMV relationship. Since laryngeal cleft is a rare condition and may not be known to most radiologists, its incidence is likely underestimated. It is important to note the association of laryngeal clefts with VACTERL and malrotation. In addition, it is essential not to confuse a laryngeal cleft with a tracheoesophageal fistula since the management differs. Keywords: Laryngeal cleft, Laryngotracheoesophageal cleft, VACTERL, Malrotation

VACTERL association is a heterogeneous condition that includes at least three out of six core structural defects which occur together more commonly than would be expected by chance alone. We report a rare association of VACTERL with unilateral proximal focal femoral deficiency and trisomy 18 syndrome.

Esophageal atresia with tracheoesophageal fistula (EA-TEF) is a congenital malformation typically identified during the neonate period. TEFs are classified according to their anatomic configuration. We present a case that demonstrates a unique anomaly that involves a distal TEF with proximal esophageal atresia duplication. Our case reveals the importance of preoperative planning and intraoperative exploration during this surgical procedure.

Key Clinical Message This case report describes a patient with a 22q11.2 duplication. His features, which include VACTERL association with an esophageal atresia/tracheo‐esophageal fistula and a vascular ring, expand the previously described phenotype for this duplication.

We present a rare case of simultaneous esophageal and tracheal atresia with trachea-esophageal fistula in a premature infant with VACTERL association. Although multiple surgical interventions were attempted in the management of this patient, the patient expired, reflecting the low survival rates associated with both esophageal atresia and tracheal atresia. This case highlights the difficulty and urgency in diagnosing this rare constellation of congenital anomalies.

Scrotal ectopia is a rare condition. Associated anomalies are common. We describe a neonate with ectopic scrotum with VACTERL association. This combination of anomalies is very rare.

VACTERL association (any three of vertebral, anal, cardiac, tracheo-esophageal, renal/radial and limb defects) and Prune belly syndrome(complete or partial triad of abdominal muscle deficiency, bilateral cryptorchidism and dilated urinary tract) are cngenitalmalformations affecting many body systems. These are derivatives of causally nonspecific disruptive events of the developmental fieldoccuring during early blastogenesis. Many of these cases are sporadic in families without much recurrence. These lesions may be associatedwith other malformations but concurrence of VACTERL with Prune belly syndrome is extremely rare. Routine antenatal checkup and ultrasonography can help in diagnosis of most of them. But, many times a detail autopsy examination is needed to detect the variety of malformations and categorise them into specific syndromes. We describe a rare combination of VCTERL with Prune bellysyndrome and many associated anomalies of a 28 weeks neonate delivered vaginally by a 37 years second gravida.

Prune belly syndrome is a rare abnormality; its association with VACTERL is even rarer. This association has been reported in literature a few times since first reported in 1993 and so far the majority have either been stillbirths or died shortly after birth. We present a case of Prune belly syndrome associated with VACTERL who is now one year old.

Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus.A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Clinical Genetics between 1985 and 2010 by perinatologists, (child) neurologists or pediatricians. Patients with hydrocephalus secondary to other pathology were excluded from this survey. We classified patients with primary congenital hydrocephalus into two main groups: non-syndromic hydrocephalus (NSH) and syndromic hydrocephalus (SH). Seventy-five individuals met the inclusion criteria, comprising 36% (27/75) NSH and 64% (48/75) SH. In 11% (8/75) hydrocephalus was familial. The cause of hydrocephalus was unknown in 81% (61/75), including all patients with NSH. The male-female ratio in this subgroup was 2.6:1, indicating an X-linked factor other than the L1CAM gene. In the group of SH patients, 29% (14/48) had a known cause of hydrocephalus including chromosomal abnormalities, L1 syndrome, Marden-Walker syndrome, Walker-Warburg syndrome and hemifacial microsomia.We performed this survey in order to evaluate current knowledge on the genetic etiology of primary congenital hydrocephalus and to identify new candidate genes or regulatory pathways for congenital hydrocephalus. Recommendations were made concerning the evaluation and genetic workup of patients with primary congenital hydrocephalus. We conclude that further molecular and functional analysis is needed to identify new genetic forms of congenital hydrocephalus. (C) 2011 Elsevier Masson SAS. All rights reserved.

The diagnosis of VACTERL syndrome can be elusive, especially in the prenatal life, due to the presence of malformations that overlap those present in other genetic conditions, including the Fanconi anemia (FA). We report on three VACTERL cases within two families, where the two who arrived to be born died shortly after birth due to severe organs' malformations. The suspicion of VACTERL association was based on prenatal ultrasound assessment and postnatal features. Subsequent chromosome breakage analysis suggested the diagnosis of FA. Finally, by next-generation sequencing based on the analysis of the exome in one family and of a panel of Fanconi genes in the second one, we identified novel FANCL truncating mutations in both families. We used ectopic expression of wild-type FANCL to functionally correct the cellular FA phenotype for both mutations. Our study emphasizes that the diagnosis of FA should be considered when VACTERL association is suspected. Furthermore, we show that loss-of-function mutations in FANCL result in a severe clinical phenotype characterized by early postnatal death.

We herein report the case of a 22-year-old Caucasian man with known vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies (VACTERL) association who presented with a headache and vertigo following the sudden and temporary loss of consciousness while attending a concert four days before admission to the hospital. On a physical examination, the following findings were found: a low body height, low-set ears, thoracic scoliosis and a mild holosystolic heart murmur. A neurosonological examination revealed a partial subclavian steal phenomenon. CT angiography of the neck vessels and aortic arch confirmed an anomalous right subclavian artery -known as the lusorian artery. Further studies are warranted in patients with VACTERL in order to identify possible links between the prevalence of an aberrant right subclavian artery (lusorian artery) and possible congenital subclavian steal syndrome or dysphagia lusoria. In addition, duplex ultrasound of the carotid and vertebral arteries may be performed as part of screening examinations in patients with congenital syndromes.

Mitochondrial DNA depletion syndromes are an important cause of mitochondrial cytopathies in both children and adults. We describe a newborn with multiple congenital malformations including a right aberrant subclavian artery and a trachea-oesophageal fistula in whom mitochondrial depletion syndrome was unmasked by perioperative muscle relaxation. After vecuronium infusion, the infant developed an irreversible postoperative paralysis, leading to death 32 days after surgery. The present case highlights (a) the clinical heterogeneity of mitochondrial depletion syndrome; (b) the importance of rigorous antemortem and postmortem investigations when the cause of a severe myopathy is uncertain; (c) the possible coexistence of mitochondrial depletion syndrome and congenital malformations as a result of a likely abnormal antenatal embryofetal development and (d) the importance of a careful anaesthetic management of children with mitochondrial depletion syndrome, which could be prone to complications related to the possible depressive effects on mitochondrial electron transport chain mediated by some anaesthetic agents.

Objective To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs).Design A population-based case-control study.Setting Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008.Population The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13371 controls with recognised syndromes or chromosomal abnormalities.Methods Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications.Main outcome measures Adjusted ORs for pregnancy-related risk factors for ARM.Results The ARM cases were more likely to be firstborn than the controls (OR1.6, 95%CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR3.9, 95%CI 1.3-11.6; OR3.4, 95%CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR5.1, 95%CI 1.7-15.6).Conclusions This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL.

Background: VATER association was first described in 1972 by Quan and Smith as an acronym which identifies a non-random co-occurrence of Vertebral anomalies, Anal atresia, Tracheoesophageal fistula and/or Esophageal atresia, Radial dysplasia. It is even possible to find out Cardiovascular, Renal and Limb anomalies and the acronym VACTERL was adopted, also, embodying Vascular, as single umbilical artery, and external genitalia anomalies. Methods: Data on patients with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) admitted in the Neonatal Intensive Care Unit (NICU) between January 2003 and January 2013 were evaluated for the contingent occurrence of typical VACTERL anomalies (VACTERL-type) and non tipical VACTERL anomalies (non-VACTERL-type). The inclusion criterion was the presence of EA with or without TEF plus two or more of the following additional malformations: vertebral defects, anal atresia, cardiovascular defects, renal anomalies and lower limb deformities, like radial dysplasia. Results: Among 52 patients with EA/TEF, 20 (38,4%) had isolated EA and 7 (21,8%) had a recognized etiology such a syndrome and therefore were excluded. Among 32 infants with EA and associated malformations, 15 (46,8%) had VACTERL association. The most common anomalies were congenital heart defects (73,3%), followed by vertebral anomalies (66,6%). Many patients also had additional non-VACTERL-type defects. Single umbilical artery was the most common one followed by nervous system abnormalities and anomalies of toes. Between the groups of infants with VACTERL type and non-VACTERL-type anomalies, there are several overlapping data regarding both the tipically described spectrum and the most frequently reported non-VACTERL-type malformations. Thus, it is possible to differentiate infants with a full phenotype (VACTERL full phenotype) and patients that do not meet all the criteria mentioned above, but with some homologies with the first group (VACTERL partial phenotype). Conclusion: The high frequency of non-VACTERL-type anomalies encountered in full and partial phenotype patients would suggest the need for an extension of the clinical criteria for the diagnosis of VACTERL association and also for pre- and post-operative management and follow-up in the short and long term.

Saeid Aslanabadi1, Kamyar Ghabili2, Mohsen Rouzrokh3, Mohammad Bagher Hosseini1, Masoud Jamshidi1, Farzad Hami Adl4, Mohammadali M Shoja51Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz; 2Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz; 3Department of Pediatric Surgery, Mofid Hospital, Shaheed Beheshti University of Medical Sciences, Tehran; 4Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz; 5Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, IranBackground: Predicting the presence of long-gap esophageal atresia (EA) prior to the surgery is of clinical importance. No comparison between short-gap and long-gap EA for the prevalence of VACTERL and non-VACTERL-type anomalies has yet been performed.Objective: The aim of this study was to compare VACTERL and non-VACTERL-type anomalies between patients with short-gap and long-gap EA.Methods: Retrospectively, medical records of all newborns managed for EA/tracheoesophageal fistula (TEF) in Tabriz Children's Hospital and Tehran Mofid Hospital between 2007 and 2010 were evaluated. Demographic data and associated anomalies including both the VACTERL and non-VACTERL-type defects were listed. The VACTERL spectrum defects covered vertebral/costal, anorectal, cardiovascular, TEF, and renal- or radial-type limb anomalies. The non-VACTERL-type anomalies included hydrocephalus, orofacial defects, respiratory system anomalies, gastrointestinal anomalies, genital anomalies, and non-VACTERL limb defects. Demographic data, and the VACTERL and non-VACTERL-type anomalies were compared among children with long-gap EA and those with short-gap EA.Results: Two hundred and seventy-six children were included in the study: 230 (83.3%) in the short-gap EA group and 46 (16.7%) in the long-gap EA group. Although prevalence of the VACTERL spectrum anomalies did not differ between the two groups, the non-VACTERL anomaly was more common in the long-gap EA group (P = 0.02). Among the VACTERL-type defects, TEF was detected in 30 (65.2%) and 218 (94.7%) patients in long-gap and short-gap EA groups, respectively (P = 0.0001).Conclusion: The non-VACTERL-type anomalies, but not the VACTERL spectrum defects, are more frequent in patients with long-gap EA than those with short-gap EA.Keywords: esophageal atresia, short-gap, long-gap, tracheoesophageal fistula, anomaly, VACTERL

Contains fulltext : 97495.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Urological anomalies are frequently seen in patients with anorectal malformations (ARM) and can result in upper urinary tract deterioration. Whether the current method of screening is valid, adequate and needed for all patients is not clear. We, therefore, evaluated the urological screening methods in our ARM patients for changes in urological treatment, outcome and follow-up. METHODS: The medical records of 331 children born with an ARM in the period 1983-2003 were retrospectively studied. Documentation of diagnosis, screening method, urological anomalies, treatment, complications, follow-up and outcome were measured. RESULTS: The overall incidence of urological anomalies was 52%. The incidence of urological anomalies and urological follow-up time decreased with diminishing complexity of the ARM. Hydronephrosis, vesico-urethral reflux, lower urinary tract dysfunction and urinary incontinence were encountered most. Treatment invasiveness increased with the increase of complexity of an ARM. Lower urinary tract dysfunction needing urological care occurred in 43% in combination with lumbosacral or spinal cord anomalies and in 8% with no abnormalities in the lumbosacral-/spinal region. CONCLUSIONS: Urological anomalies in patients with complex ARM are more severe than in patients with less complex ARM. Ultrasonography of the urinary tract should be performed in all patients. Voiding cysto-urethrography can be reserved for patients with dilated upper urinary tracts, urinary tract infections or lumbosacral and spinal abnormalities. All patients with complex ARM need urodynamic investigations. When using these indications, the screening for urological anomalies in ARM patients can be optimized with long-term follow-up in selected patients.

Esophageal atresia and tracheoesophageal fistula (EA/TEF) are major congenital malformations affecting 1:3500 live births. Current research efforts are focused on understanding the etiology of these defects. We describe well-known animal models, human syndromes, and associations involving EA/TEF, indicating its etiologically heterogeneous nature. Recent advances in genotyping technology and in knowledge of human genetic variation will improve clinical counseling on etiologic factors. This review provides a clinical summary of environmental and genetic factors involved in EA/TEF.

International audience; Objective: To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy Methods: French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. Results: Spondylarthropathies (n = 8), rheumatoid arthritis (n = 4), juvenile idiopathic arthritis (it = 2), and psoriatic arthritis (n = 1) were treated by infliximab (n = 3), adalimumab (n = 2), or etanercept (n = 10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. Conclusion: The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth. (C) 2008 Elsevier Masson SAS. All rights reserved.

BACKGROUND Some factors(s)/features(s) of maternal insulin-dependent diabetes mellitus are considered common human teratogens. Although the variable association of cardiac, renal, and skeletal anomalies are commonly observed in infants from diabetic mothers, the relationship between VACTERL (i.e., the association of vertebral and cardiac defects, tracheo-esophageal fistula, renal/radial malformations, and other limb anomalies) and maternal diabetes has not been sufficiently emphasized in the literature. CASE We report on a 3-year-old boy presenting with a constellation of blastogenetic malformations strongly suggestive of VACTERL association. His mother was affected by insulin-dependent diabetes since she was 7 years old and pregnancy history disclosed very high glucose and HbA1c levels, especially during the first 2 gestational months. CONCLUSIONS In an attempt to properly counsel the parents, we reviewed the literature and identified four additional patients with VACTERL and first trimester exposure to maternal diabetes mellitus. Although this evidence does not strongly support a causal relationship between these two conditions, additional arguments may substantiate this hypothesis. The pathogenesis of diabetic embryopathy in relation to the VACTERL phenotype is also discussed.