Anomalies Of Other Organ Systems Research Articles

Genetics of anomalies of the kidney and urinary tract with congenital heart disease: A review.

Congenital anomalies of the kidney and urinary tract (CAKUT) and congenital heart disease (CHD) are the most common congenital defects and constitute a major cause of morbidity in children. Anomalies of both systems may be isolated or associated with congenital anomalies of other organ systems. Various reports support the co-occurrence of CAKUT and CHD, although the prevalence can vary. Cardiovascular anomalies occur in 11.2% to 34% of patients with CAKUT, and CAKUT occur in 5.3% to 35.8% of those with CHD. The co-occurrence of genetic factors in both CAKUT and CHD would raise common etiologies including genetics, genetic-environmental interactions, or shared molecular mechanisms and pathways such as NODAL, NOTCH, BMP, WNT, and VEGF. Studies in animal models and humans have indicated a genetic etiology for CHD and CAKUT with hundreds of genes recognized and thousands of entries, found in a catalog of human genetic disorders. There are over 80 CAKUT genes and over 100 CHD genes available for clinical testing. For example, the HNFIB gene accounts for 5% to 31% of reported cases of CAKUT. In view of the association between CAKUT and CHD, a thorough cardiac examination should be performed in patients with CAKUT, and a similar evaluation for CAKUT in the presence of CHD. This will allow early diagnosis and therapeutic intervention to improve the long- term outcome of patients affected, and test for at-risk family members. We present here evidence for an association of anomalies involving the two organ systems, and discuss possible etiologies of targeted genes, their functions, biological processes and interactions on embryogenesis.

Accuracy of Multimodality Fetal Imaging (US, MRI, and CT) for Congenital Musculoskeletal Anomalies.

Ultrasonography (US) is the first-line diagnostic tool used to assess fetal musculoskeletal (MSK) anomalies. Associated anomalies in other organ systems may benefit from evaluation via Magnetic Resonance Imaging (MRI). In this study, we compared the diagnostic accuracy of US and MRI to diagnose fetal MSK (primary objective) and non-MSK anomalies (secondary objective). We describe additional findings by low-dose computerized tomography (CT) in two cases incompletely characterized via US and MRI. This was an IRB-approved retrospective study of consecutive patients with suspected fetal MSK anomalies examined between December 2015 and June 2020. We compared individual MSK and non-MSK anomalies identified via US, MRI, and CT with postnatal outcomes. Sensitivity and specificity for US and MRI were calculated and compared. A total of 31 patients with 112 MSK and 43 non-MSK anomalies were included. The sensitivity of MRI and US for MSK anomalies was not significantly different (76.6% vs. 61.3%, p = 0.3). Low-dose CT identified eight additional skeletal anomalies. MRI diagnosed a higher number of non-MSK anomalies compared to US (81.4% vs. 37.2%, p < 0.05). Fetal MRI and US have comparable sensitivity for MSK anomalies. In selected cases, low-dose CT may provide additional information. Fetal MRI detected a larger number of non-MSK anomalies in other organ systems compared to US. Multimodality imaging combining all the information provided by MRI, US, and CT, if necessary, ultimately achieved a sensitivity of 89.2% (95% CI: 83.4% to 95.0%) for the diagnosis of musculoskeletal anomalies and 81.4% for additional anomalies in other organs and systems.

Congenital diaphragmatic hernia: a case series in tertiary care centre

Congenital diaphragmatic hernia (CDH) is the presence of a defect in the diaphragm that allows the herniation of the abdominal viscera into the thorax. The mortality is the result of persistent pulmonary hypertension and respiratory insufficiency due to abnormal pulmonary vessels and hypoplastic lungs. The incidence of congenital diaphragmatic hernia is 1 in 2500 births. The etiology of congenital diaphragmatic hernia remains unclear. It is thought to be multifactorial with genetic, environmental, and/or nutritional factors playing a role. CDH can be an isolated anomaly or associated with anomalies in other organ systems. The most frequent aneuploidies associated with CDH include trisomy 18, trisomy 13, trisomy 21, and less frequently Turner syndrome (45, X). Exposure to teratogenic agents like mycophenolate mofetil, allopurinol, and lithium during pregnancy is reported to be associated with CDH. Recently, studies indicate disturbances in the retinoid-signaling pathway as a potential cause of CDH. This case series aims to pull importance of a viable protocol for antenatal evaluation of CDH, and meanwhile to underline the importance of a good interdisciplinary antenatal evaluation of these cases for the fetal outcome.

Mayer‐Rokitansky‐Küster‐Hauser syndrome presented as recurrent urinary tract infection in childhood (case report)

AbstractBackgroundMayer‐Rokitansky‐Küster‐Hauser syndrome (MRKH) is characterized by the absence of the uterus and upper two‐thirds of the vagina, normal secondary sexual development, and 46XX karyotype is one of the rare types of Mullerian agenesis. There may be associated congenital anomalies in other organ systems especially those with the same embryogenesis such as the urinary tract mostly in its upper parts present in 40% of cases including renal agenesis, ectopic kidney (unilateral or bilateral), renal hypoplasia, horseshoe kidneys, and hydronephrosis. Other organ systems also may be affected such as skeletal and auditory systems. MRKH is diagnosed mostly during or after adolescence because of unexpected amenorrhea or disturbed sexual experiences.Case reportWe present a 3‐year‐old girl coming with recurrent bouts of urinary tract infections diagnosed as having MRKH syndrome established by imaging and genetic studies. Our case is very rare and interesting because it presents itself as a recurrent urinary tract infection in early childhood which is rare and unusual. In this case, early detection helped us to prevent chronic kidney disease and also planning to perform necessary minimal but very important surgical procedures before initiation of sexual activities to relieve the psychosocial aspect of the syndrome both for the child and parents.ConclusionHealth givers should keep in mind that rare syndromes may present as a repeated quite common problem or have confusing or conceiving presentations. This point will assist us in the early detection of rare diseases at an earlier age or stage.

Renal agenesis

Renal agenesis

Congenital anomalies in children with postneonatally acquired cerebral palsy: an international data linkage study.

To describe the major congenital anomalies present in children with postneonatally acquired cerebral palsy (CP), and to compare clinical outcomes and cause of postneonatally acquired CP between children with and without anomalies. Data were linked between total population CP and congenital anomaly registers in five European and three Australian regions for children born 1991 to 2009 (n=468 children with postneonatally acquired CP; 255 males, 213 females). Data were pooled and children classified into mutually exclusive categories based on type of congenital anomaly. The proportion of children with congenital anomalies was calculated. Clinical outcomes and cause of postneonatally acquired CP were compared between children with and without anomalies. Major congenital anomalies were reported in 25.6% (95% confidence interval [CI] 21.7-29.9) of children with postneonatally acquired CP. Cardiac anomalies, often severe, were common and present in 14.5% of children with postneonatally acquired CP. Clinical outcomes were not more severe in children with congenital anomalies than those without anomalies. Cause of postneonatally acquired CP differed with the presence of congenital anomalies, with cerebrovascular accidents predominating in the anomaly group. Congenital anomalies were likely associated with cause of postneonatally acquired CP in 77% of children with anomalies. In this large, international study of children with postneonatally acquired CP, congenital anomalies (particularly cardiac anomalies) were common. Future research should determine specific causal pathways to postneonatally acquired CP that include congenital anomalies to identify opportunities for prevention. One-quarter of children with postneonatally acquired cerebral palsy (CP) have a major congenital anomaly. Cardiac anomalies, often severe, are the most common anomalies. Causes of postneonatally acquired CP differ between children with and without congenital anomalies.

Abstract 14975: Increased Morbidity and Mortality in Patients With Hypoplastic Left Heart Syndrome and Genetic Abnormalities

Introduction: Hypoplastic left heart syndrome (HLHS) is a genetically heterogenous, severe form of congenital heart disease. Hypothesis: Patients with reported genetic abnormalities will have worse outcomes than those without reported genetic abnormalities. Methods: This was a retrospective review of patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase I registry. Registry enrollment occurred at discharge following stage 1 palliation. Patients were placed into one of three groups: major syndromes (Turner, Down, CHARGE, DiGeorge, Jacobsen, VATER, heterotaxy), other genetic abnormality, or no reported genetic abnormality. Demographic and clinical variables were compared using Pearson Chi-square, one-way ANOVA, or Kruskal-Wallis test. Tukey post-hoc test was applied to adjust p-values for pairwise group comparisons. Outcomes of length of stay, death, and combined outcomes of death, not a candidate for stage 2 palliation and transplant were compared among the groups. Results: Of the 2182 patients, major syndromes were reported in 110 (5%), other genetic abnormalities in 126 (5.8%) and no abnormalities in 1946 (89.2%). Those with major syndromes weighed less at birth and the time of stage I palliation, were more likely to be female and have a primary cardiac diagnosis of unbalanced AVC. Those with major syndromes or other genetic abnormalities were more likely to have moderate to severe AV valve regurgitation, moderate to severe ventricular dysfunction, arrhythmia requiring therapy, and major anomalies of other organ systems compared to those with no abnormalities. Patients with no reported genetic abnormalities reached full oral feeds sooner after the Norwood (19 vs 24 days), were more likely to be discharged on all oral feeds (75% vs 59% and 62%) and were discharged earlier (35 vs 45 and 43 days). For the outcome of death, there was no significant difference among the groups. The combined outcome of death, not a candidate for stage 2 palliation, and heart transplant was more likely in those with a major syndrome after adjusting for covariates. Conclusions: Patients with HLHS and major syndromes or other genetic abnormalities experience greater morbidity and mortality during the interstage period.

Long-term urologic and gynecologic follow-up and the importance of collaboration for patients with anorectal malformations

Anorectal malformations (ARM) are well recognized to be associated with anomalies in other organ systems. The introduction of screening protocols has increased the diagnosis of these anomalies and greater collaboration with other specialties has influenced the treatment and follow-up of patients with ARMs. Much of the medical literature regarding the treatment of anorectal malformations has focused on technical details of operations and early post-surgical outcomes. Recently, an increase in published data regarding the long-term sequelae of an ARM diagnosis has resulted in an emphasis extended follow up in this population. Patient support groups have highlighted complex issues in ARM patients persist into adulthood have advocated for improved transitional care. This article describes the benefits of long-term follow-up and identifies key issues in ARM patients with respect to urologic and gynecologic health. A collaborative model of care is outlined and suggested timings of screening for potential problems is described.

A Review of Mullerian Anomalies and Their Urologic Associations

Structural anomalies of the female reproductive tract, known as Mullerian anomalies, can occur in isolation or in association with anomalies of other organ systems. Due to shared embryology, the most common association in up to 40% of patients is with renal, ureteral, and bladder anomalies. Affected girls can have a wide range of genitourinary symptoms with urologists playing an integral role in their diagnosis and treatment. To facilitate the recognition and management of these conditions, we provide a review of Mullerian anomalies including the embryology, classifications, syndromes, evaluation, and treatments with attention to their urologic applicability.

A rare case of lobulated complete renal fusion with multiple hila and vasculature.

Complete renal fusion without crossed renal ectopia denotes the medial fusion of the renal parenchyma (with or without changes in the microarchitecture) in the pelvis with anteriorly placed short ureters terminating into the bladder. This could be due to the failure of renal analgen to ascent, lateral migration, axial rotation, and persistence of primitive vascular supply. Though remain asymptomatic such cases warrant concomitant congenital anomalies of other organ systems as well as the microarchitecture changes in the renal parenchyma.

Caudal Regression Syndrome

Caudal regression syndrome (CRS), also known as caudal dysplasia syndrome, is a rare malformation that ranges from mild coccygeal to severe forms of lumbosacral and lower thoracic agenesis. Anomalies of other organ systems may also be found simultaneously. Recognition of CRS is important as the extent of abnormality and gestational age could determine the pregnancy’s outcome. Antenatal diagnosis is possible by recognizing the characteristic features on sonography. In this particular case study, a diagnosis of CRS was made during the second trimester with sonography and resulted in an adequate medical management decision. The sonographic features of CRS and its differential diagnoses are discussed in the context of this case study.

Treatment of Children with Anorectal Malformations—10-Year Review

Introduction: Anorectal malformations include a wide spectrum of congenital defects of the anus, anal canal and rectum, which are often combined with urogenital tract defects. They are often associated with congenital anomalies of other organ systems such as genitourinary, cardiovascular, digestive, skeletal, etc. Objectives: This study aimed to review the patients with anorectal malformations, diagnosis, different types of associated anomalies and their frequency, modalities of treatment, results of treatment and complications. Materials and Methods: Since 2010, we have performed a combined retrospective and prospective analysis of a total of 76 patients with anorectal malformations which were diagnosed and treated at our clinic between 2005 and 2014. Results: Of 76 patients with anorectal malformations, 48 were male (63.16%) and 28 female (36.84%). Anal stenosis was the commonest type (30.26%) followed by ARM without fistula (25.00%) and rectourethral fistula (18.42%). The most common associated anomalies were urogenital (49.12%), cardiovascular (21.05%), gastrointestinal (15.79%), and bone malformations (5.26%). 34 patients (44.74%) were treated primarily without colostomy. In 40 patients (52.63%) colostomy was performed after birth. PSARP was the procedure of choice in 76.92% of patients. 7 patients (9.21%) died in total. Constipation was present in 52.38% of all patients. Patients older than 3 years of age totally continent were 30.91%. Redo operations were performed in 5 patients (7.94%). Conclusion: Early diagnosis of anorectal malformations is very important. Some malformations such as anal stenosis are sometimes diagnosed beyond the neonatal age. Challenging problem still remains high percentage of children that suffer from fecal incontinence and constipation.

Renal Fusion Anomalies: A Review of Surgical Anatomy

Congenital renal fusion anomalies, characterized by either partial or complete fusion of the two kidneys, are represented by horseshoe kidney, crossed renal ectopia with fusion and fused pelvic cake kidney. Though these anomalies may remain asymptomatic, in certain cases they may be associated with pathological conditions like nephrolithiasis, hydronephrosis, recurrent urinary tract infections, vesicoureteral reflux and renal neoplasms. Concomitant congenital anomalies involving other organ systems observed with some renal fusion anomalies make them important clinical entities. Thorough knowledge of these renal fusion anomalies, associated renovascular abnormalities, pathologies and anomalies of other organ systems are most essential for appropriate patient management by urologists, surgeons, vascular surgeons and radiologists alike. This review focuses on the surgical anatomy of various renal fusion anomalies, their incidence, anatomical, radiological and pathological features and associated anomalies in the light of available literature.

Late Diagnosis of Anorectal Malformations in Children

Anorectal malformations (ARM) include a wide spectrum of congenital defects of the anus, anal canal and rectum, which are often associated with congenital anomalies of other organ systems. They appear with different clinical presentations ranging from simple imperforate anal membrane to very complex defects. They are usually detected immediately after birth or early at neonatal age, but some patients with the milder defects are diagnosed at a later age. Objectives: The aim of this study is to analyze the incidence of patients with ARM diagnosed after neonatal period, clinical features and consequences of delayed diagnosis. Materials and Methods: Since 2010 we performed a combined retrospective and prospective analysis of a total of 76 patients with anorectal malformations, diagnosed and treated at our clinic between 2005 and 2014. We analyzed patients’ age at the time of diagnosis, sex, type of defect, associated anomalies and postoperative functional outcome. Results: 18 patients with ARM (23.68%) were diagnosed beyond the neonatal period. Of them 11 were female (61.11%) and 7 male patients (38.89%). The earliest diagnosed patient was a male of three months of age, while the latest diagnosed patient was a female of 8.5 years of age. All patients had low type anomalies, presented with anal stenosis (16), perineal fistula (1) and vestibular fistula (1). Six patients (33.33%) were also diagnosed with associated anomalies. Conclusion: High incidence of delayed diagnosis of ARM highlights the importance of a careful, comprehensive clinical examination of the perineum of newborns. All patients with severe and chronic constipation must be evaluated for eventually missed diagnosis of low type anorectal malformations.

QUERATODERMIA PALMOPLANTAR EPIDERMOLÍTICA (TIPO VÖRNER) - CARACTERIZAÇÃO DE UMA FAMÍLIA E REVISÃO DA LITERATURA

A queratodermia palmoplantar epidermolítica (queratodermia de Vörner) é uma doença da queratinização autossómica dominante caracterizada por espessamento difuso e não-transgressivo das regiões palmoplantares, na ausência de anomalias ectodérmicas associadas. Deve-se a mutações no gene da queratina 9 (KRT9) e, mais raramente, no gene da queratina 1 (KRT1). Apresentamos o caso de uma doente do sexo feminino (caso índice), com 16 meses de idade e filha de pais não-consanguíneos, que apresentava, desde o segundo mês de vida, hiperqueratose difusa com superfície amarelada e bordo eritematoso, limitada às superfícies palmares e plantares. As unhas, dentes, cabelo e mucosas eram normais e não se evidenciavam alterações noutros sistemas orgânicos. A investigação clínica permitiu identificar um total de 15 elementos da família com quadro clínico similar, sendo o ancestral comum um trisavô da mãe de origem italiana. Efectuou-se uma biópsia cutânea lesional na mãe, a qual mostrou marcada hiperqueratose ortoqueratótica e epidermólise da epiderme média e superior. O padrão de hereditariedade, o aspecto clínico e os achados histológicos eram compatíveis com o diagnóstico de queratodermia palmoplantar hereditária do tipo Vörner. Foi instituído tratamento com creme contendo ureia a 20% na criança e ureia a 30-50% na mãe com melhoria clínica satisfatória.

The Collaborative Cross as a resource for modeling human disease: CC011/Unc, a new mouse model for spontaneous colitis.

Inflammatory bowel disease (IBD) is an immune-mediated condition driven by improper responses to intestinal microflora in the context of environmental and genetic background. GWAS in humans have identified many loci associated with IBD, but animal models are valuable for dissecting the underlying molecular mechanisms, characterizing environmental and genetic contributions and developing treatments. Mouse models rely on interventions such as chemical treatment or introduction of an infectious agent to induce disease. Here, we describe a new model for IBD in which the disease develops spontaneously in 20-week-old mice in the absence of known murine pathogens. The model is part of the Collaborative Cross and came to our attention due to a high incidence of rectal prolapse in an incompletely inbred line. Necropsies revealed a profound proliferative colitis with variable degrees of ulceration and vasculitis, splenomegaly and enlarged mesenteric lymph nodes with no discernible anomalies of other organ systems. Phenotypic characterization of the CC011/Unc mice with homozygosity ranging from 94.1 to 99.8 % suggested that the trait was fixed and acted recessively in crosses to the colitis-resistant C57BL/6J inbred strain. Using a QTL approach, we identified four loci, Ccc1, Ccc2, Ccc3 and Ccc4 on chromosomes 12, 14, 1 and 8 that collectively explain 27.7 % of the phenotypic variation. Surprisingly, we also found that minute levels of residual heterozygosity in CC011/Unc have significant impact on the phenotype. This work demonstrates the utility of the CC as a source of models of human disease that arises through new combinations of alleles at susceptibility loci.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-013-9499-2) contains supplementary material, which is available to authorized users.

Improved antenatal detection of congenital anomalies in women with pre‐gestational diabetes: population‐based cohort study

To compare antenatal detection of congenital anomaly in women with and without pre-gestational diabetes and their pregnancy outcomes in a regional cohort study. Data from a total of 7148 singleton pregnancies with a congenital anomaly delivered between 1 January 1996 and 31 December 2008 were extracted from the Northern Diabetes in Pregnancy and Northern Congenital Abnormality Surveys. Antenatal ultrasound detection rates of congenital anomaly in pregnancies complicated by major non-chromosomal congenital anomaly and resulting in live birth, stillbirth, late miscarriage (20-23 weeks of gestation) or termination of pregnancy for a congenital anomaly, were compared between women with and without diabetes (120 and 7028, respectively). A significantly higher rate of antenatal detection of congenital anomalies was observed in women with diabetes compared with women without diabetes (50.8 vs. 38.6%, respectively; relative risk 1.32; 95% CI 1.10-1.57; P = 0.003). Cardiovascular anomalies were the only group with a significantly higher antenatal detection rate in women with diabetes (31.8 vs. 10.4%; relative risk 3.05; 95% CI 1.95-4.76; P < 0.00001). This difference remained after excluding cases of ventricular septal defect (52.2 vs. 16.3%; relative risk 3.20; 95% CI 2.13-4.80; P < 0.0001). Among women with diabetes, male fetal sex was the only factor associated with a higher antenatal detection rate. There were no differences in the rates of termination of pregnancy, late miscarriage, stillbirth or infant death between groups. Antenatal detection of cardiovascular anomalies was higher in women with diabetes, suggesting that recommendations for enhanced cardiovascular scanning may improve detection. Greater awareness of the increased risk of anomalies in other organ systems is needed.

Cloacal exstrophy with vesicoureteric junction obstruction: Rare association

Cloacal exstrophy is an extremely rare congenital abnormality resulting in an exstrophy of the urinary, intestinal and genital organs and associated with anomalies of other organ systems. We report a complicated case of cloacal exstrophy associated with right vesicoureteric junction obstruction.

Hirschsprung's disease in the north of england: prevalence, increasing trends, associated anomalies and survival

BackgroundHirschsprung's disease is the commonest congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut, which causes intestinal obstruction. Few studies report its...

Cloacal Exstrophy: A Case Report and Literature Review

Cloacal exstrophy is an extremely rare congenital malformation resulting in an exstrophy of the urinary, intestinal, and genital organs and associated with anomalies of other organ systems. We present a complicated case of cloacal exstrophy and the recent progress in the management of this probably most complicated anomaly in pediatric urology and surgery.