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

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

Umbilical Appendix Masquerading as a Patent Omphalomesenteric Duct in a Neonate.

The umbilicus is the site of a number of well-recognized and unusual abnormalities. Well-known neonatal umbilical abnormalities include umbilical hernias, granulomas/polyps, and congenital remnants of development. In this article, we describe a rare case of an appendix draining through the umbilicus of a neonate. In the literature, there are only 15 cases with possible umbilical appendix. We describe this rare case along with a review of the literature and discuss the underlying pathophysiology.

Co-occurring non-omphalocele and non-gastroschisis anomalies among cases with congenital omphalocele and gastroschisis.

The pathogenesis of omphalocele and gastroschisis is not obvious. Their etiology is disputed. The prevalence and the types of anomalies co-occurring with omphalocele and gastroschisis are variable in the different series published. The aim of this study was to estimate the frequency and the types of co-occurring anomalies in cases with gastroschisis and omphalocele. This study was performed in a well-described population of 387,067 consecutive births between 1979 and 2007. Hundred-one cases with omphalocele were registered (2.61 per 10,000), 75 (74.3%) had co-occurring anomalies comprising chromosomal anomalies (28 cases, 27.7%, including 18 trisomy 18), non-chromosomal syndromes (16 cases, 15.8%, including 3 cases with Beckwith-Wiedemann syndrome, 2 cases with the OEIS sequence, and one case with the Pentalogy of Cantrell complex), and 31 cases, 30.7% with MCA (multiple congenital anomalies). The most common MCA were musculoskeletal (23.5%), urogenital (20.4%), cardiovascular (15.1%), and central nervous (9.1%). Seventy-one cases of gastroschisis were ascertained (1.83 per 10,000). However, the prevalence increased during the study period. The frequency was highest in the mothers 15-19 years old. Sixteen out of the 71 cases with gastroschisis, (22.5%) had co-occurring anomalies including 11 cases of MCA and 5 cases with syndromes. To conclude, the frequency and the types of anomalies co-occurring with omphalocele and gastroschisis are peculiar. Therefore, cases with gastroschisis and omphalocele need to be screened for co-occurring anomalies.

Investigation of a connection between abdominal wall defects and severity of the herniation in fetuses with gastroschisis and omphalocele.

Analyze the biometric parameters and the size (area) of abdominal wall defect (AWD) in fetuses with gastroschisis and omphaloceles and correlate them with the herniated internal organs. We studied 22 fetuses (11 with AWDs and 11 without anomalies). In all fetuses we evaluated the xiphopubic distance (XPD) and iliac crest distance (ICD). In fetuses with AWDs we dissected the abdominal wall and measured the width and length of the defect for calculating its area and studying the correlation between the size of the defect with the organs that were herniated. For statistical analysis, the Anova and Tukey post-test were used (p < 0.05). The XPD in the control group had mean of 4.2 mm (2.3-5.9; SD ± 1.11), while in the AWDs it was 4.2 mm (2.9-5.5; SD ± 0.98) (p = 0.4366). The ICD had mean values of 2.5 mm (1.6-3.4; SD ± 0.58) in the control group, and 2.3 mm (1.2-3.0; SD ± 0.56) in AWDs fetuses (p = 0.6963). The number of herniate organs do not have significant correlation with the area of the defect (r2 = 0.2504, p = 0.5068). There is no correlation between the size (area) of abdominal wall defects and the number of the internal organs that herniated. Therefore, the hole size is not a predictor of the severity of the gastroschisis or omphalocele.

Antibiotic Utilization and Infection Among Infants with Abdominal Wall Defects.

BACKGROUND: Neonates with abdominal wall defects are at an increased infection risk because of the defect itself and prolonged neonatal intensive care unit (NICU) stays. Antibiotic prophylaxis until closure of the defect is common. However, infection risk and antibiotic use have not been well quantified in these infants. METHODS: A retrospective cohort study of infants with abdominal wall defects (gastroschisis and omphalocele) admitted to a single-center NICU from 2007 to 2018. Demographic and clinical information, including microbiologic studies, antibiotic dosing and surgical care, were collected. Antibiotic use was quantified using days of therapy (DOT) per 1000 patient-days. Sepsis was defined as culture of a pathogen from a normally sterile site. RESULTS: Seventy-four infants were included; 64 (86%) with gastroschisis and 10 (14%) with omphalocele. Median day of closure was 8 days [interquartile range (IQR) 6-10, range 0-31]. All infants received ≥1 course of antibiotics; median antibiotic DOT/infant was 24.5 (IQR 18-36) for an average of 416.5 DOT per 1000 patient-days. Most antibiotic use was preclosure prophylaxis (44%) and treatment of small intestinal bowel overgrowth (24%). Suspected and proven infection accounted for 26% of all antibiotic use. Skin and soft tissue infection (13/74, 18%) and late-onset sepsis (11/74, 15%) were the most common infections; 2 infants had sepsis while on antibiotic prophylaxis. All infants survived to discharge. CONCLUSIONS: Most antibiotic use among infants with abdominal wall defects was prophylactic. Infection on prophylaxis was rare, but 35% of infants had infection after prophylaxis. Improved stewardship strategies are needed for these high-risk infants.

Letter to the Editor: Case of Appendix Incarcerated in an Umbilical Hernia.

Umbilical hernias and acute appendicitis are common general surgical problems, but an appendix incarcerated in an umbilical hernia is quite rare. We present a case of such and briefly review the available literature on the topic. We conclude that future authors should include a minimum set of information in such case reports or case series so that readers can gain as much as possible from our collective experience with this uncommon problem.

Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis.

BACKGROUND: Pseudodiastrophic dysplasia (PDD) is a severe skeletal dysplasia associated with prenatal manifestation and early lethality. Clinically, PDD is classified as a 'dysplasia with multiple joint dislocations'; however, the molecular aetiology of the disorder is currently unknown. METHODS: Whole exome sequencing (WES) was performed on three patients from two unrelated families, clinically diagnosed with PDD, in order to identify the underlying genetic cause. The functional effects of the identified variants were characterised using primary cells and human cell-based overexpression assays. RESULTS: WES resulted in the identification of biallelic variants in the established skeletal dysplasia genes, B3GAT3 (family 1) and CANT1 (family 2). Mutations in these genes have previously been reported to cause 'multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects' ('JDSCD'; B3GAT3) and Desbuquois dysplasia 1 (CANT1), disorders in the same nosological group as PDD. Follow-up of the B3GAT3 variants demonstrated significantly reduced B3GAT3/GlcAT-I expression. Downstream in vitro functional analysis revealed abolished biosynthesis of glycosaminoglycan side chains on proteoglycans. Functional evaluation of the CANT1 variant showed impaired nucleotidase activity, which results in inhibition of glycosaminoglycan synthesis through accumulation of uridine diphosphate. CONCLUSION: For the families described in this study, the PDD phenotype was caused by mutations in the known skeletal dysplasia genes B3GAT3 and CANT1, demonstrating the advantage of genomic analyses in delineating the molecular diagnosis of skeletal dysplasias. This finding expands the phenotypic spectrum of B3GAT3-related and CANT1-related skeletal dysplasias to include PDD and highlights the significant phenotypic overlap of conditions within the proteoglycan biosynthesis pathway.

Operative versus conservative treatment for giant omphalocele: Study of French and Ivorian management.

INTRODUCTION: The giant omphalocele is currently a surgical challenge. The morbidity and mortality associated with its care is non-negligible. Nowadays, different studies have revived the debate between conservative and surgical management for giant omphalocele. The purpose of this study is to compare the conservative and surgical management of the giant omphalocele in terms of morbidity and mortality. METHODS: Retrospective study including all giant omphaloceles comparing surgical management (French University hospital centers) and tanning (Ivory Coast University hospital center). Epidemiology was studied as well as medical and surgical managements both intra and post operative. RESULTS: One hundred and forty-seven patients included (98 patients in the "tanning" group and 49 in the "surgery" group). Hospital length of stay is significantly shorter in the "tanning" group as they do not spend time in intensive care unit. Morbidity is higher in "surgery" group. The average duration for oral empowerment was acquired at 179 days in the "surgery" group, whereas in the "tanning" group 90% was immediately and exclusively breastfed. No significant differences in terms of epithelialization time. CONCLUSION: The tanning treatment has its own place in the therapeutic arsenal in the management of the giant omphalocele no matter where it takes place. However, its realization in surgical environments prevents certain complications related to the technique or the pathology.

Trisomy 18 in a First-Trimester Fetus with Thoraco-Abdominal Ectopia Cordis.

Introduction: Fetuses with trisomy 18 will occasionally also have ectopia cordis. Case report: A routine ultrasound scan at 12 weeks' gestation revealed a large fetal anterior thoraco-abdominal wall defect with an extrathoracic heart and a liver-containing omphalocele. Chorionic villus sampling revealed a 47,XY,+18 karyotype. Additional anomalies detected after termination of the pregnancy included a cleft lip and palate and left radial agenesis. Conclusions: The prenatal diagnosis of ectopia cordis associated with aneuploidy can be made in the first trimester of pregnancy. An extrathoracic heart located in a liver-containing omphalocoele should be considered a thoraco-abdominal ectopia cordis rather than pentalogy of Cantrell.

Kagami-Ogata syndrome in a fetus presenting with polyhydramnios, malformations, and preterm delivery: a case report.

BACKGROUND: Kagami-Ogata syndrome is also known as paternal uniparental disomy 14 and related disorders and is caused by abnormal genomic imprinting in the long arm of the chromosome 14q32.2 region. Its clinical manifestations include polyhydramnios in the fetal stage, respiratory insufficiency because of a small thorax, abdominal wall abnormalities, and peculiar facial features after birth. CASE PRESENTATION: A 38-year-old Japanese primigravida woman was referred to our hospital in the 19th week of pregnancy for suspected omphalocele. She had a history of hypothyroidism but was prescribed orally administered levothyroxine (50 µg/day) prior to conception and was euthyroid. Her ultrasound scan prior to visiting our hospital revealed fetal omphalocele, heavy for date, and polyhydramnios. The mother was advised to be admitted for observation from 28 weeks of gestation for threatened premature delivery. She required amniodrainage at 29 and 32 weeks of gestation. At 35 weeks of gestation, the fetal membrane prematurely ruptured and she gave birth after an emergency Cesarean section. The infant was a male child with a birth weight of 3188 g, and was suspected to have Kagami-Ogata syndrome after birth based on thoracic hypoplasia, swallowing function abnormalities, and peculiar facial features. A definitive diagnosis was established by performing genetic testing of the infant after obtaining informed written consent from both the parents; the results of the genetic testing revealed hypermethylated intergenic-differentially methylated region and maternally expressed gene 3-differentially methylated region in the corresponding chromosome 14 region. Both the parents were genetically tested after adequate genetic counseling, which revealed a de novo microdeletion in a differentially methylated region. CONCLUSION: Kagami-Ogata syndrome should have been suspected because of the presence of polyhydramnios and omphalocele during pregnancy. Respiratory insufficiency soon after birth, because of a small thorax, is expected in this disease and a diagnosis during pregnancy may have enabled appropriate care after birth.

Primary Umbilical Hernia Repair: A Large-Volume Single-Surgeon Study.

There are conflicting views regarding techniques for repair of small umbilical hernias (UHs). Here, we compare the recurrence rate in primary repair with that reported for mesh repair by examining a single surgeon's practice at a large medical center with a comprehensive electronic medical record. A six-year retrospective review of primary UH repairs between January 2012 and December 2017 at Kaiser Permanente Los Angeles Medical Center was undertaken. Patients were identified through a database search of the electronic medical record. The primary endpoint of UH recurrence was examined; median follow-up was 3.4 years. Primary, elective UH repair was performed in 244 patients; 71 per cent of hernias were small (<2 cm). The total number of recurrences was seven (3%). The t test analysis showed significant differences in the average size of hernia defects between those with recurrences (2 cm) and those without (1.4 cm), P < 0.05. Primary repair affords low infection and recurrence rates, comparable to those reported for mesh repair. Our single-surgeon/large-volume study contributes to the evidence that primary UH repair is a safe and durable method, with low risk of recurrence. The use of absorbable monofilament suture, and selection for lower BMI and smaller hernia sizes proved to be effective.

The validity of the viscero-abdominal disproportion ratio for type of surgical closure in all fetuses with an omphalocele.

OBJECTIVE: To determine the predictive value of the fetal omphalocele circumference/abdominal circumference (OC/AC) ratio for type of surgical closure and survival and to describe the trajectory of OC/AC ratio throughout gestation. METHODS: This cohort study included all live-born infants prenatally diagnosed with an omphalocele in our tertiary centre (2000-2017) with an intention to treat. The OC/AC ratio and liver position were determined using 2D ultrasound at three periods during gestation (11-16, 17-26, and/or 30-38 weeks). Primary outcome was type of closure; secondary outcome was survival. In the secondary analyses, the predictive value of the OC/AC-ratio trend for type of closure and survival was assessed. RESULTS: Primary closure was performed in 37/63 (59%) infants, and 54/63 (86%) survived. The OC/AC ratio was predictive for type of closure and survival in all periods. Optimal cut-off values for predicting closure decreased throughout gestation from 0.69 (11-16 weeks) to 0.63 (30-38 weeks). Repeated OC/AC-ratio measurements were available in 33 (73%) fetuses. The trend of the OC/AC ratio throughout gestation was not significantly associated with type of closure. All infants without liver herniation underwent primary closure. CONCLUSION: Type of omphalocele surgical closure and survival can be predicted prenatally on the basis of the OC/AC ratio and liver herniation independent of associated anomalies. LEARNING OBJECTIVE: The reader will be able to use the OC/AC ratio throughout gestation in all omphalocele cases for prediction of type of closure and survival and thus patient counselling.

[Early diagnosis of omphalocele: Prognostic value of the herniated viscera for associated anomalies]. / Omphalocèle au premier trimestre : valeur pronostique du contenu extériorisé pour le risque d'anomalie associée.

OBJECTIVES: Prognosis of infants with omphalocele depends on many factors, including associated anomalies. "Small" omphaloceles are believed to have more often WB syndrome, but so far no prenatal criterion has been demonstrated to predict associated anomalies. The aim of this study was to assess the outcomes of omphaloceles with prenatal diagnosis, and to seek for any correlation between the herniated viscera in the first trimester and the risk of associated anomalies. METHODS: We conducted a retrospective study at the Necker Enfants Malades Hospital between 2008 and 2018. Pregnancy outcomes and post natal data were collected and compared to the omphalocele content in the first trimester. RESULTS: One hundred and ninety-one women with antenatal diagnosis of omphalocele were included. Twenty-eight percent were isolated at birth, 32% had a polymalformative syndrome with chromosomal anomaly, 13% had a polymalformative syndrome without genetic anomaly, 9% had a Wiedemann-Beckwith syndrome, 7% had an association with cardiopathy, 6% had a limb body wall complex, 3% had OEIS complex and one case had a Cantrell pentalogy. The presence of the liver in the omphalocele during the first trimester was a predictive factor of heart disease (85.7% vs 48.6% P=0.01). The presence of bowel in the omphalocele during the first trimester was a predictor of chromosomal abnormalities (69.6% vs 37.2% P<0.001). Omphalocele content in the first trimester was not predictive of Wiedemann-Beckwith syndrome. CONCLUSION: Ultrasound analysis in the first trimester of omphalocele content is a valuable clue for prenatal counseling and diagnosis of associated abnormalities.

Congenital fistulisation of Meckel's diverticulum in omphalocele sac: case report.

Fistulisation of Meckel's diverticulum in the top of an omphalocele sac is very rare. To our Knowledge, three cases were reported in the literature. We presente in this report a new case of this uncommon presentation.

Outcomes in omphalocele correlate with size of defect.

BACKGROUND: Omphaloceles can be some of the more challenging cases managed by pediatric surgeons. Single center studies have not been meaningful in delineating outcomes due to the length of time required to accumulate a large enough series with historical changes in management negating the results. The purpose of this study was to evaluate factors impacting the morbidity and mortality of neonates with omphaloceles. METHODS: A multicenter, retrospective observational study was performed for live born neonates with omphalocele between 2005 and 2013 at nine centers in the United States. Maternal and neonatal data were collected for each case. In-hospital management and outcomes were also reported and compared between neonates with small and large omphaloceles. RESULTS: Two hundred seventy-four neonates with omphalocele were identified. The majority were delivered by cesarean section with a median gestational age of 37 weeks. Overall survival to hospital discharge was 81%. The presence of an associated anomaly was common, with cardiac abnormalities being the most frequent. Large omphaloceles had a significantly longer hospital and ICU length of stay, time on ventilator, number of tracheostomies, time on total parenteral nutrition, and time to full feeds, compared to small omphaloceles. Birth weight and defect size were independent predictors of survival. CONCLUSION: This is the largest contemporary study of neonates with omphalocele. Increased defect size is an independent predictor of neonatal morbidity and mortality. LEVEL OF EVIDENCE: Level II.

Retrospective analysis of smaller than 3-cm umbilical hernia repair with the lightweight macroporous mesh.

There is evidence that mesh repair for primary umbilical hernias results in fewer recurrences and similar wound complication rates compared to tissue repair. Various devices and surgical approaches are used in umbilical hernia repair. The ULTRAPRO PLUG (UPP) has been adopted for inguinal hernias and femoral hernias with excellent results. However, there are few reports on the use of UPP for umbilical hernia repair. Thus, the aim of this study was to evaluate efficacy and safety in the treatment of smaller than 3-cm umbilical hernias using the UPP.The medical records of 123 patients who underwent umbilical hernia repair using the UPP between October 2011 and September 2017 were reviewed. All patients were followed-up after 1 month and later in 2018. Demographics, surgical information, and immediate postoperative and long-term complications were assessed.Out of 123 patients, there were 37 male and 86 female patients with a mean age of 50.6 years. The median duration of hernia surgery was 20.5 min (range, 12-34), and 109 (88.6%) patients underwent day surgery. The median defect diameter was 1.4 cm (range, 0.5-3). No mortality or major complications occurred during the perioperative period. Long-term follow-up data were available for 107 (87.0%) patients. The median follow-up duration was 33 months (range, 5-76 months). Early postoperative complications included 1 case of seroma, 2 cases of fat liquefaction, and 1 case of superficial surgical site infection. During follow-up, there were 2 recurrences, 1 case of chronic mesh infection, and 2 patients with chronic postoperative pain.The ULTRAPRO PLUG offers a simple and quick means of repairing smaller than 3-cm umbilical hernias with lower recurrence rates and fewer postoperative complications.

Mice doubly deficient in Six4 and Six5 show ventral body wall defects reproducing human omphalocele.

Omphalocele is a human congenital anomaly in ventral body wall closure and may be caused by impaired formation of the primary abdominal wall (PAW) and/or defects in abdominal muscle development. Here, we report that mice doubly deficient in homeobox genes Six4 and Six5 showed the same ventral body wall closure defects as those seen in human omphalocele. SIX4 and SIX5 were localized in surface ectodermal cells and somatic mesoderm-derived mesenchymal and coelomic epithelial cells (CECs) in the PAW. Six4-/-;Six5-/- fetuses exhibited a large omphalocele with protrusion of both the liver and intestine, or a small omphalocele with protrusion of the intestine, with complete penetrance. The umbilical ring of Six4-/-;Six5-/- embryos was shifted anteriorly and its lateral size was larger than that of normal embryos at the E11.5 stage, before the onset of myoblast migration into the PAW. The proliferation rates of surface ectodermal cells in the left and right PAW and somatic mesoderm-derived cells in the right PAW were lower in Six4-/-;Six5-/- embryos than those of wild-type embryos at E10.5. The transition from CECs of the PAW to rounded mesothelial progenitor cells was impaired and the inner coelomic surface of the PAW was relatively smooth in Six4-/-;Six5-/- embryos at E11.25. Furthermore, Six4 overexpression in CECs of the PAW promoted ingression of CECs. Taken together, our results suggest that Six4 and Six5 are required for growth and morphological change of the PAW, and the impairment of these processes is linked to the abnormal positioning and expansion of the umbilical ring, which results in omphalocele.