Wide Spectrum Of Congenital Anomalies Research Articles

Characteristic craniofacial defects associated with a novel USP9X truncation mutation

Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.

The bloated ear drum- A unique case of bullous myringitis

Otological conditions range from a wide spectrum of congenital anomalies to inflammations, infections and complicated tumours that often not much is said about simple conditions such as myringitis. Bullous myringitis is not just a very unique condition but it also associated with a much-dreaded condition in the form of sudden SNHL and needs immediate diagnosis and timely treatment. Here we present to you one such case report and the management.

Aortic Arch Variants and Anomalies: Embryology, Imaging Findings, and Clinical Considerations.

There is a wide spectrum of congenital anomalies or variations of the aortic arch, ranging from non-symptomatic variations that are mostly detected incidentally to clinically symptomatic variations that cause severe respiratory distress or esophageal compression. Some of these may be accompanied by other congenital heart diseases or chromosomal anomalies. The widespread use of multidetector computed tomography (CT) in clinical practice has resulted in incidental detection of several variations of the aortic arch in adults. Thus, radiologists and clinicians should be aware of the classification of aortic arch anomalies and carefully look for imaging features associated with a high risk of clinical symptoms. Understanding the embryological development of the aortic arch aids in the classification of various subtypes of aortic arch anomalies and variants. For accurate diagnosis and precise evaluation of aortic arch anomalies, cross-sectional imaging modalities, such as multidetector CT or magnetic resonance imaging, play an important role by providing three-dimensional reconstructed images. In this review, we describe the embryological development of the thoracic aorta and discuss variations and anomalies of the aortic arch along with their clinical implications.

Surgical validation of functional magnetic resonance urography in the study of ureteral anomalies distal to the uretero-pelvic junction in a pediatric cohort.

Ureteral anomalies distal to the Uretero-Pelvic Junction (UPJ) belong to the wide spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). They can cause severe obstruction requiring a detailed anatomical depiction to define the surgical approach. Up to date, ultrasonography, voiding cystourethrography and scintigraphy are considered the gold-standard diagnostic tools to study obstructive anomalies of the urinary tract, however, they do not provide accurate ureteral anatomical details. The aim of our study was to evaluate the concordance between functional magnetic resonance urography (fMRU) and intraoperative findings to define ureteral anomalies distal to UPJ. Pediatric patients with ureteral anomalies distal to the UPJ who underwent surgery after performing fMRU were retrospectively collected. Surgical data were compared with radiological results. The concordance was assessed considering both pathological and non-pathological urinary tracts and was calculated by means of the Cohen's kappa coefficient. fMRU diagnostic accuracy was defined by sensitivity, specificity, and binomial exact confidence intervals. We included 46 patients. The sensitivity and specificity of fMRU were 98.0% and 83,3%; positive predictive value 90,4%, negative predictive value 96.2%. The concordance between surgical findings and fMRU was 92,3%, with a k Cohen's coefficient of 0.83 (excellent). Our study demonstrates the excellent agreement between fMRU and surgical findings in the definition of ureteral anomalies distal to the UPJ in children. Thus, it could be considered a valid imaging technique in the preoperative planning as it provides the surgeon with important information regarding the etiology and site of the obstruction.

Rare Antenatal Fetal Malformations of the Anterior Abdominal Wall in Mali: About a Case

Abdominal wall malformations correspond to a wide spectrum of congenital anomalies that are due to a defect in the closure of the anterior abdominal wall and can be fatal. We report the case of laparoschisis associated with a poly malformation syndrome in the same fetus at the reference health center of commune III of the district of Bamako. The objective is to clarify the interest of antenatal ultrasound in the diagnosis and prognosis of these malformations. It was a 19-year-old prim gravid woman received as part of the prenatal check-up. Antenatal ultrasound had allowed the diagnosis of malformation of the anterior abdominal wall of the gastroschisis type associated with abnormalities of the neural tube, the urogenital system and the bone skeleton. The antenatal diagnosis of the malformations had motivated the realization of a therapeutic termination of pregnancy at 19 weeks of amenorrhea and 3 days by triggering and vaginal delivery, allowing the confirmation of the diagnosis of gastroschisis and the poly malformation syndrome which is extremely rare. Antenatal ultrasound remains an ideal means of imaging for monitoring pregnancy and had made it possible to make the prognosis and antenatal diagnosis of multiple malformations in association, and to indicate better therapeutic decision-making.

CLASSIC FINDING OF DANDY-WALKER MALFORMATION- CASE REPORT

Summary: The frequency and importance of posterior fossa evaluation has increased signicantly in the last 20 years due to advances in neuroimaging. Today, conventional and advanced neuroimaging techniques allow a detailed assessment of the complex anatomical structures within the posterior fossa. A wide spectrum of congenital anomalies (anomalies due to an alteration of the primary developmental program caused by a genetic defect) and due to the breakdown of a structure that had a potential for normal development has been demonstrated. Knowledge of the spectrum of congenital anomalies of the posterior fossa and its well-dened diagnostic criteria is essential for optimal therapy, an accurate prognosis, and correct genetic counseling. Objective: Analyze the importance of the precise diagnosis of congenital anomalies of the posterior fossa, emphasizing Dandy Walker syndrome, through a clinical case. Design: Prospective, observational in a single center. Methodology: This is a systematic review, Dandy Walker syndrome, detailing its clinical characteristics and short-term complications. The information and images obtained belong to the medical personnel in charge of the case, whose reinforcements are provided by the Excel, Word and JPG statistical package.

A Homozygous Dab1-/- Is a Potential Novel Cause of Autosomal Recessive Congenital Anomalies of the Mice Kidney and Urinary Tract.

This study aimed to explore morphology changes in the kidneys of Dab1−/− (yotari) mice, as well as expression patterns of reelin, NOTCH2, LC3B, and cleaved caspase3 (CASP3) proteins, as potential determinants of normal kidney formation and function. We assumed that Dab1 functional inactivation may cause disorder in a wide spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). Animals were sacrificed at postnatal days P4, P11, and P14. Paraffin-embedded kidney tissues were sectioned and analyzed by immunohistochemistry using specific antibodies. Kidney specimens were examined by bright-field, fluorescence, and electron microscopy. Data were analyzed by two-way ANOVA and t-tests. We noticed that yotari kidneys were smaller in size with a reduced diameter of nephron segments and thinner cortex. TEM microphotographs revealed foot process effacement in the glomeruli (G) of yotari mice, whereas aberrations in the structure of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) were not observed. A significant increase in reelin expression, NOTCH2, LC3B and cleaved CASP3 proteins was observed in the glomeruli of yotari mice. Renal hypoplasia in conjunction with foot process effacement and elevation in the expression of examined proteins in the glomeruli revealed CAKUT phenotype and loss of functional kidney tissue of yotari.

Congenital Abdominal Wall Defects: A Topic Review and a Case Report of a Lethal Polymalformation Syndrome with a Giant Abdominoschisis

Abstract Abdominal wall defects (AWDs) represent a wide spectrum of congenital anomalies which are characterized by a herniation of abdominal organs through a pathologic opening in the abdominal region. The author describes a 29-year-old pregnant woman who was prenatally found to have a living female fetus with a giant omphalocele and a spinal deformation in the lumbosacral region. An evisceration of the abdominal contents into the amnionic cavity was visible. Based on USG findings the limb-body wall complex was suggested. An amniocentesis was performed and a genetic testing identified a chromosome 17q23.1–q23.2 duplication. As the fetal anomaly was considered incompatible with life, a medical termination of the pregnancy was carried out. Postmortem examination of the fetus revealed a huge abdominoschisis with a complete evisceration of the liver, stomach, small and large intestines, spleen, and the right kidney. A severe left-sided scoliosis deformity of the spine with crooked trunk was evident. The gross findings shared the features of omphalocele and limb-body wall complex with no postnatal life expectancy. Most fetal AWDs have poor prognosis. The pathology of these conditions differ greatly and require specific prenatal evaluation and pregnancy management for each entity. Accurate assessment of AWDs will allow the identification of isolated forms with better clinical outcomes compared to associated multiple malformations with chromosomal anomalies or genetic syndromes.

Ventral Abdominal Wall Defects.

1. Sara A. Mansfield, MD, MS* 2. Tim Jancelewicz, MD, MA, MS* 1. *Division of Pediatric Surgery, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN Clinicians should be aware of the strategies for prenatal and postnatal management of infants with omphalocele and gastroschisis. After completing this article, readers should be able to: 1. Recognize the implications and differences in management between gastroschisis and omphalocele. 2. Review the initial stabilization and management of infants with omphalocele and gastroschisis. 3. Review the surgical management options and rationale for infants with ventral abdominal wall defects. Abdominal wall defects represent a wide spectrum of congenital anomalies. These can range from lethal limb-body wall syndrome to benign umbilical cord hernias. Gastroschisis and omphalocele are the 2 most common defects and are the focus of this review. Although both of these diseases affect the umbilical area, they differ widely in their underlying pathogenesis, genetics, and associated disorders. Consequently, their management techniques and outcomes are quite different. This article reviews the pathogenesis, genetics, diagnostics, and outcomes for each disease, followed by an in-depth review of recent management updates. ### Pathogenesis Omphalocele (or exomphalos) is a herniation of the abdominal viscera through a midline abdominal wall defect (Fig 1). This defect is located at the base of the umbilical stalk, and herniated viscera are covered by a 3-layer membrane of peritoneum, Wharton jelly, and amnion. This contrasts with umbilical cord hernias, which are covered by intact skin and contain only a small protrusion of abdominal contents, and gastroschisis, which has no covering at all and occurs to the right of midline (Table). Omphaloceles are present in approximately 1 per 1,100 pregnancies. However, there is a high rate of spontaneous abortion, making the incidence of omphalocele per live birth approximately 1 per 4,000 to 1 per 6,000. (1) …

Rubinstein-Taybi syndrome: New neuroradiological and neuropsychiatric insights from a multidisciplinary approach.

Rubinstein-Taybi syndrome is a rare, autosomal dominant, plurimalformative disorder that is clinically characterized by intellectual disability and a wide spectrum of congenital anomalies; facial dysmorphisms are typical, and broad thumbs and great toes are particularly distinctive. Its genetic basis is only partially known, with a detection rate of approximately 65-70%; specifically, microdeletions or mutations in the CREBBP or EP300 genes can be found. Much is known about its clinical features and health-care protocols, but some areas of clinical knowledge are currently unsolved. In particular, few efforts have been made until now to understand the variability in the neuropsychological and neurobehavioral profile and to deepen knowledge of the neuroradiological malformative pattern. Consequently, little is known about the possible genotype-phenotype correlations of these issues. Here, we report clinical and genetic data from a cohort of 23 RSTS Italian patients. The most common features in brain magnetic resonance imaging (MRI) were dysmorphic aspects of the corpus callosum (73.6%) with or without minor dysmorphisms of cerebellar vermis, periventricular posterior white matter hyperintensity, and other less common anomalies. The most interesting feature on the whole spine MRI scans was the tendency for a low-lying conus medullaris without terminal filum thickening. These data will help to improve neuropsychiatric and neuroradiological knowledge and highlight specific genotype-phenotype correlations.

Atypical microdeletion in 22q11 deletion syndrome reveals new candidate causative genes

Rationale:22q11 deletion syndrome, the most common chromosomal microdeletion disease, is caused by megabase-sized deletions on chromosome 22q11.2. It is characterized by a wide spectrum of congenital anomalies in velopharyngeal and facial, cardiac, genitourinary, vertebroskeletal, respiratory, digestive, and central nervous systems. Phenotype–genotype studies have revealed several causative genes that regulate the development of the third and fourth pharyngeal arches in human. However, the exact pathogenesis of this syndrome remains unknown. Herein, we report a case of 22q11 deletion syndrome with an atypical microdeletion of 125 kb.Patient concerns:A 15-year-old Chinese girl presented with symptoms of facial dysmorphia, cardiac defects, velopharyngeal insufficiency, splenomegaly, immunodeficiency, and thrombocytopenia.Diagnoses:Microarray analysis revealed a 22q11.23 deletion of 125 kb (chromosome 22: 24276973–24402263), suggesting the diagnosis of 22q11 deletion syndrome. The haploinsufficient genes included GSTT2B, GSTT2, DDTL, DDT, GSTTP1, LOC391322, GSTT1, and GSTTP2.Interventions:The patient was administrated glucocorticoids and calcium supplements.Outcomes:No epistaxis or petechiae episode occurred during the follow-up; her platelet count ranged between 60 × 109 and 80 × 109/L.Lessons:Although none of the previous reported causative genes were affected in the patient, her clinical manifestations were typical of 22q11 deletion syndrome, apart from her progressive splenomegaly. This case indicated 8 new candidate pathogenic genes for 22q11 deletion syndrome. Given that the loss of these genes was sufficient to induce 22q11DS defects, whether these genes directly influence the pathogenesis of 22q11DS or through interactions with known hotspot mutations is worthy of research.

Genotyping Fanconi anemia patients from Serbia reveals three novel FANCD2 variants

Fanconi anemia is rare inherited disease characterized by wide spectrum of congenital anomalies, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. Molecular genetic analysis of mutations in FANC genes is of a great importance for diagnosis confirmation, prenatal and carrier testing, as well as for prediction of chemotherapy outcome and disease complications. In this study we performed screening of frequently affected regions of FANCD2 gene for sequence variants in six unrelated FA-D2 patients in Serbia. This is the first molecular analysis of FANCD2 gene in Serbian FA-D2 patients. A total of 10 sequence variants were detected, one in homozygous, and nine in heterozygous state. Two variants were found within exons, and eight within introns, in deep intronic regions. In-silico analysis showed that among all detected variants one exon variant and three intron variants might have impact on splicing mechanism. Heterozygous variants found in intron 3, c.206-246delG; exon 26, c.2396 C>A and intron 28, c.2715+573 C>T were not previously reported. In-silico analysis revealed that among them, two (intron 3, c.206-246 delG and exon 26, c.2396 C>A) could be novel disease-causing mutations. Many variants were found in more than one patient, including those unreported, indicating their possible ethnic association. Great number of variants in some patients suggests their non-random emergence in Fanconi anemia pathway.

Oculoauriculovertebral spectrum with radial anomaly in child

Oculoauriculovertebral spectrum (OAVS) or Goldenhar syndrome is a wide spectrum of congenital anomalies that involves structures arising from the first and second branchial arches. It is characterized by a wide spectrum of symptoms and physical features. These abnormalities mainly involve the cheekbones, jaws, mouth, ears, eyes, or vertebrae. Other conditions with ear and/or radial involvement, such as, the Nager syndrome, Holt-Oram syndrome, Radial–renal syndrome, facioauriculoradial dysplasia, Fanconi anemia, and Vertebral, Anal atresia, Cardiac, Trachea, Esophageal, Renal, and Limb (VACTERL) association should be considered for differential diagnosis. Here we report a child who had facial asymmetry, microsomia, microtia, congenital facial nerve palsy, conductive hearing loss, skin tags, iris coloboma, and preaxial polydactyly.

562 Radiological Evaluation of Pediatric Congenital Urinary Tract Anomalies

PurposeTo illustrate a wide spectrum of congenital anomalies of the urinary tract in children.Materials and MethodsWe demonstrate radiological evaluation and its clinical significance of congenital anomalies of the urinary tract...

Uncorrected Rectovestibular Fistula and Pregnancy: A Management Dilemma

Abstract Background: Anorectal malformations (ARM) represent a wide spectrum of congenital anomalies in which the anus fails to open normally onto the perineum. In females, the most common ARM is an imperforate anus with a rectovestibular fistula. There are limited data available on the optimal management of an uncorrected rectovestibular fistula in pregnancy. Case: A 23-year-old gravida 3, para 2, living, 1, with a history of fecal incontinence since birth and of passing stools through the orifice near the vestibular region, was admitted at 34+3 weeks' gestation for evaluation of ARM. On examination, a prominent skin tag was present at the anal dimple with normal gluteal fold and a fistulous opening in the region of vestibule with minimal prolapse of rectal mucosa. The patient underwent an elective cesarean section with sterilization at 38+3 weeks' gestation in view of having had two previous cesarean sections. Results: Her postnatal period was uneventful and she was discharged on the 7th postoperative d...

Cell Death Serves as a Single Etiological Cause of a Wide Spectrum of Congenital Urinary Tract Defects

We genetically disrupted the wolffian duct in mice to study the affected organogenesis processes and to test the hypothesis that cell loss can be the developmental basis for a wide spectrum of congenital anomalies in the kidney and urinary tract. We used Hoxb7-Cre transgenic lines (HC1 and HC2) to induce diphtheria toxin production from a ROSA(DTA) allele, disrupting the wolffian duct and derivatives. The first set of mutants (HC1;ROSA(DTA/+)) exhibited agenesis of the kidney, ureter and reproductive tracts. The second set of mutants (HC2;ROSA(DTA/+)) exhibited diverse defects, including renal agenesis/hypoplasia, hydronephrosis, hydroureter, ureter-vas deferens fistulas in males and ureter-oviduct/uterus fistulas in females. The phenotypic differences correspond to the degree of apoptosis induced caudal truncation of the wolffian duct, which is less severe and more variable in HC2;ROSA(DTA/+) mice. Whenever the wolffian duct failed to reach the urogenital sinus, the ureter failed to separate from the wolffian duct, suggesting that ureteral migration along the common nephric duct to the cloaca and the subsequent common nephric duct degeneration constitute the only pathway for separating the ureter and wolffian duct derivatives. The diverse and severe defects observed emphasize the central role of the wolffian duct in providing progenitors and signals for urogenital development. These results also indicate that the quantitative difference in cell death induced caudal truncation of the wolffian duct can lead to a wide range of qualitatively distinct defects, and that cell death can serve as a single etiological cause of a wide spectrum of congenital kidney and urinary tract defects.

Clinical, cytogenetic and molecular-cytogenetic characterization of a patient with a de novo tandem proximal-intermediate duplication of 16q and review of the literature

Partial trisomy 16 is rare and most of the reported cases are secondary to chromosome rearrangements resulting in concurrent monosomies or trisomies of a second chromosome. Only a few patients survive the neonatal period and the duplication of the long arm seems to be mainly responsible for the prenatal lethality of the full trisomy 16. The reported patients with a partial 16q trisomy have a wide spectrum of congenital anomalies that include dysmorphic features, central nervous system malformations, failure to thrive, and club feet. The patients with duplications of proximal 16q frequently have short stature, developmental delay, speech delay, learning difficulties, and mild to severe behavioral problems. Here we describe a patient with an inverted de novo tandem duplication of 16q with breakpoints evaluated in detail by molecular-cytogenetic techniques. Main clinical features include postural, motor and speech delay with severe learning difficulties and behavioral problems, obesity, microcephaly, and mild dysmorphic features. In the report we attempt to classify the few reported patients with pure partial duplications of 16q in more narrow and homogeneous groups: proximal, proximal-intermediate, intermediate, and intermediate-distal duplications. Moreover, we emphasize the importance of proper cytogenetic investigation and complete molecular cytogenetic refinement in all cases with a suspected chromosomal anomaly.

Spina bifida occulta in children: presentation and outcome

Background Occult spinal dysraphism (OSD) encompasses a wide spectrum of congenital anomalies. Since OSD can lead to irreversible neurological, urological and orthopedic dysfunction, early diagnosis and treatment is necessary. In this study we evaluated a selected cohort of patients with OSD with regard to presenting symptoms and clinical outcome. The main purpose of this project is to develop clinical guidelines for this condition. Materials and methods We retrospectively reviewed the medical records of all children with OSD referred to University Hospital Uppsala during the period 2000-2008. Fifty-six Children (22 males and 34 females) aged from 3 days to 16 years were identified having OSD. All had MR scans carried out. The median observation time was 11 years. Results The first sign of neurological dysfunction was noticed at the median age of two years. The symptoms included deformities of feet, bladder dysfunction and gait disturbance. Retrospectively, cutaneous lesions in the back were found in 43 children. The MR scans demonstrated in all children various congenital anomalies such as diastematomyelia or lipomyelomeningocele. During the follow-up period deterioration was seen in approximately half of the patients. Twenty-eight children underwent detethering operation. Despite this operation the symptoms of eight of these children progressed. At follow-up at the median age of 11 years 38 children had clinical signs and symptoms of neurological dysfunction whereof 19 children had severe persistent symptoms. Conclusions In this study one third of the children with OSD developed persistent severe symptoms of neurological dysfunction. It is highly important to detect these lesions before the occurrence of neurological or urological manifestations. Urinary incontinence is often the first clinical symptom, but can be difficult to evaluate when the child is very young.

Angiotensin II Type 2 Receptor Gene Polymorphism in Caucasian Children With a Wide Spectrum of Congenital Anomalies of the Kidney and Urinary Tract

The A-1332G transition of the angiotensin II type 2 receptor (AT2R) gene was found to occur more often in males with ureteropelvic (UPJO) or ureterovesical junction obstruction (UVJO). However, other studies have shown controversial results. Tauhe frequency of this polymorphism was investigated in 275 Caucasian children (153 boys, 122 girls) with a wide spectrum of congenital anomalies both of upper (165) and lower (110) urinary tract system and in 200 controls (100 boys, 100 girls). Among the included malformations, renal agenesis and duplex collecting system (DCS) were studied for the first time. The frequency of the G allele did not differ among patients (193 of 397 total alleles, 48.6%) and controls (146 of 300, 48.7%). No significant difference was also found in the frequency of the G allele in subgroups of congenital uropathies compared with controls. When analysis was performed in males and females separately, no significant difference was found in the frequency of the G allele in male (45.1%) or female (50.8%) patients compared with male (57.0%) or female (44.5%) controls. Our data indicate that the AT2R gene A-1332G transition is not associated with the development of human congenital uropathies and further investigations should be carried out to unravel their etiology.

Prenatal Diagnosis of Complete Trisomy 9: A Case Report and Review of the Literature

Complete trisomy 9 is a very rare chromosome aneuploidy, associated with specific patterns of multisystem dysmorphism and a wide spectrum of congenital anomalies. We present a case of complete trisomy 9 with prenatal sonographic findings in the second trimester. The combination of sonography and karyotyping from cordocentesis enabled us to establish the prenatal diagnosis. An additional clinical feature of this syndrome that has not been reported previously is an aortopulmonary communication. A review of the literature specifically dealing with prenatal sonographic findings with complete trisomy 9 is also presented.