Congenital malformations

Congenital malformations are single or multiple defects of the morphogenesis of organs or body districts identifiable at birth or during the intrauterine life. Their global birth prevalence is about 2–3%. Both genetic and environmental factors, as well as their combination in a multifactorial contest, may induce congenital defects. Congenital malformations may be classi- fied on the basis of clinical, etiologic as well as pathogenetic criteria. Relevant diagnostic and therapeutic tools have been progressively improving in the last decades, contributing to a better identification and a reduction of long-term morbidity and mortality of these patients. A correct identification of a congen- ital defect is the first step in order to offer a helpful genetic coun- seling to the parental couple. Because of their increasing life expectancy, congenital malformations represent today a major issue in the health services for the amount of resources they need for the requested multidisciplinary assistance

The Coat-Hanger Angle Sign

An infant boy, the second child of healthy parents, was born at 35.5 weeks of gestation by cesarean delivery performed in emergency because of fetal bradycardia and polyhydramnios. At birth his weight was 2770 g (62nd percentile), length 48.3 cm (69th percentile), and head circumference 33.5 cm (64th percentile). Findings of a phys- ical examination showed a broad forehead, a depressed nasal bridge, anteverted nares, a long and protruding philtrum, a high arched palate, retrognathia, joint contractures, and an umbilical hernia. The Apgar score was 6/8 at 1/5 minutes. Because of progressive respiratory distress he required hos- pitalization and noninvasive support ventilation for the first 36 hours. At admission, a chest radiograph demonstrated a bell-shaped thorax with curved ribs and cupped anterior ends (Figure 1). These chest roentgenogram findings were further investigated by calculating the coat-hanger angle (CHA), which was 36 1 (Figure 2; available at www.jpeds. com). CHA refers to the average of the angles between the peak point of both sixth posterior ribs and the horizontal axis passing through their costovertebral articulations. If there is no peak point of the sixth posterior ribs, the center of the ribs is used instead. An upward angle is defined as +, and a downward angle as . The horizontal axis is defined as a line passing through 2 points of both sixth costovertebral junctions.1,2 If this value exceeds 34 (CHA sign), in patients with suggestive dysmorphic features, a paternal uniparental disomy 14 syndrome, recently named Kagami-Ogata syndrome (KOS), should be suspected.2,3 KOS results in a unique phenotype characterized by facial abnormalities, abdominal wall defects, placentomegaly, poly- hydramnios, and a small bell-shaped thorax with “coat- hanger” appearance of the ribs constituting its prominent pathognomonic feature.4,5 We performed a segregation study by microsatellite analysis polymorphisms using the leukocyte genomic DNA of the patient and parents, which confirmed our clinical suspicion. There are several congenital disorders wherein thoracic hy- poplasia is the sole radiological hallmark.6 The finding of a CHA sign is a well-characterized and simple feature that could suggest the diagnosis of KOS. This sign is described to be more severe than that seen in other genetic bone dis- eases and to persist from infancy through childhood/puberty. Because of a poor swallowing reflex, the patient required nasogastric feeding support until 3 weeks of age. He was discharged when he was 35 days of age

Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly and hypoplastic left middle cerebral artery

Prenatal ultrasonographic detection of unilateral cerebral ventriculomegaly arises suspicion of pathological condition related to cerebrospinal fluid flow obstruction or cerebral parenchimal pathology. Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures. Congenital and acquired types are recognized and have been described, mainly in late childhood, adolescence and adult ages. We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome. Prenatal imaging, cerebral vascular anomaly responsible for the cerebral hemiatrophy and the early clinical evolution have never been described before in such a young child and complete the acquired clinical descriptions in older children. Differential diagnosis, genetic investigations, neurophysiologic assessments, short term clinical and developmental follow up are described. Dyke-Davidoff-Masson syndrome must be ruled out in differential diagnosis of fetal unilateral ventriculomegaly. Early clinical assessment, differential diagnosis and cerebral imaging including cerebral MRI angiography allow the clinicians to diagnose also in early infancy this rare condition

Invasive pneumococcal diseases in children aged 1-59 months in sicily, Italy: Importance of active family paediatrician surveillance and vaccination coverage

Purpose: Aim of this study was to analyze pediatric invasive pneumococcal disease rates several years after the implementation of infant pneumococcal vaccination. Methods: The study was carried out in Sicily and involved about 30,000 children, aged 1-59 months, actively monitored by 100 family pediatricians during 2010 and 2011. All children who met the inclusion criteria were considered eligible, recorded using a stan-dardized case report form and investigated for the presence of S. pneumoniae in speci-mens from sterile sites. Results: None of the 40 eligible children was confirmed as a case of invasive pneumococ-cal disease. The incidence rate of invasive pneumococcal disease cases was 0.0/100,000 in both years. Regional childhood pneumococcal vaccination coverage rates were 90.7% in 2010 and 92.0% in 2011. Conclusions: Our results show that during the study period invasive pneumococcal dis-ease cases were rare in Sicilian children, suggesting a very effective control of the disease in a region with very high vaccination coverage against S. pneumoniae

Intellectual disabilitiy in developmental age

Intellectual disability (ID) is a neurodevelopmental dis- order characterized by deficits in intellectual and adap- tive functioning that present before 18 years of age [1]. ID is heterogeneous in etiology and encompasses a broad spectrum of functioning, disability, needs and strengths. Originally formulated in strictly psychometric terms as performance greater than 2.5 SDs below the mean on intelligence testing, the conceptualisation of ID has been extended to include defects in adaptive beha- viours [2]. The term-global developmental delay-(GDD) is usually used to describe children younger than 5-years of age who fail to meet expected developmental milestones in multiple areas of intellectual functioning [1]. In both conditions the symptoms must be present in the early developmental period, but they may not become fully manifest until social demands exceed patients’ capacities. ID affects 1.5 to 2% of the population in Western countries and represents an important health burden [3]. During the past decade, advances in genetic research have enabled genomewide discovery of chromosomal copy-number and single-nucleotide changes in patients with ID and autism as well as in those with other neu- rodevelopmental disorders. These technological advances-which include array comparative genomic hybridization (CGH), single nucleotide polymorphism genotyping arrays and massively parallel sequencing- have transformed the approach to the identification of etiologic genes and genomic rearrangements in the research laboratory and are now being applied in the clinical diagnostic arena [4]. In this view, the American Academy of Pediatrics recently released a guidance for the clinician in rendering Pediatric Care [5]. The sug- gested clinical approach to the patient should be con- ducted closely with a geneticist and includes the child’s medical history, the family history, the physical and neu- rologic examinations (emphasizing the dysmorphology examination) and the examination for neurologic or behavioral signs that might suggest a specific recogniz- able syndrome or diagnosis. After this clinical evalua- tion, focused use of genetic laboratory tests, imaging and other consultations are critical in establishing the right diagnosis, its pattern of inheritance and the subse- quent follow-up. Finally, this guidance highlights a renewed emphasis on array CGH, that is now considered the first-line diagnostic test for children who present with GDD/ID of unknown cause, and on the identification of-treatable-causes of GDD/ID with the recommendation to consider screening for inborn errors of metabolism [5]. The future use of whole-genome or next generation sequencing offers pro- mises and challenges needing to be yet addressed before their regular implementation in the clinic

CONGENITAL DIAPHRAGMATIC HERNIA AND ESOPHAGEAL ATRESIA: THE IMPORTANCE OF RESPIRATORY FOLLOW-UP IN CONGENITAL THORACIC MALFORMATION

Esophageal atresia, congenital diaphragmatic hernia, pulmonary function test, respiratory morbidity, Long-term follow-u

Portal Vein Thrombosis in a Preterm Newborn with Mutation of the MTHFR and PAI-1 Genes and Sepsis by Candida parapsilosis

Objective This report discusses the role of both congenital and acquired risk factors in the pathogenesis of portal vein thrombosis (PVT). Study Design We describe the clinical management and treatment of PVT in a preterm newborn with a homozygous mutation of the methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) genes and sepsis by Candida parapsilosis. Results Although literature data suggest a minor role of genetic factors in thrombophilia in the case of only one mutation, we hypothesize that combined thrombophilic genetic defects may have a cumulative effect and significantly increase the thrombotic risk. Conclusion It could be appropriate to include more detailed analyses of procoagulant and fibrinolytic factors in the diagnostic workup of neonatal thrombosis, also through the investigation of genetic polymorphisms. The anticoagulant therapy and the removal of concurrent risk factors remain basic steps for the adequate management and prevention of complications

Intrauterine growth pattern and birthweight discordance in twin pregnancies: a retrospective study

Background: Twins, compared to singletons, have an increased risk of perinatal mortality and morbidity, due mainly to a higher prevalence of preterm birth and low birthweight. Intrauterine growth restriction (IUGR) is also common and can affect one or both fetuses. In some cases, however, one twin is much smaller than the other (growth discordance). Usually, high birthweight discordance is associated with increased perinatal morbidity. The aim of this study is to describe the epidemiological features of a population of twins at birth, with particular reference to the interpretation and clinical effects of birthweight discordance. Methods: We evaluated retrospectively the clinical features of 70 infants born from twin pregnancies and assessed birthweight discordance in 31 pregnancies where both twins were followed at our institution. Discordance was treated both as a continuous and a categorical variable, using a cutoff of 18%. Possible relationships between birthweight discordance and other variables, such as maternal age, gestational age, birthweight percentile, number of SGA newborns in the pair, Hematocrit (Ht) discordance and neonatal anemia, prevalence of malformations, neonatal morbidity and death, were analyzed. Results: In our cohort birthweight percentile decreased slightly with increasing gestational age. Birthweight discordance, on the contrary, increased slightly with the increase of gestational age. A high discordance is associated to the presence of one SGA twin, with the other AGA or LGA. In our population, all 6 pregnancies in which discordance exceeded 18% belonged to this category (one SGA twin). Ht discordance at birth is associated to the presence of neonatal anemia in a twin, but it is not significantly related to weight discordance. Finally, in our case history, weight discordance is not associated in any way with the prevalence of malformations, morbidity and mortality. Conclusions: Birthweight discordance is an important indicator of complications that act asymmetrically on the two fetuses, affecting intrauterine growth in one of them, and usually determining the birth of a SGA infant. Our case history shows a significant statistical association between pair discordance and IUGR in one of the twins, but we could not demonstrate any relationship between discordance and the prevalence of malformations, morbidity and mortality