Identification of Genetic Variants Associated with Hereditary Thoracic Aortic Diseases (HTADs) Using Next Generation Sequencing (NGS) Technology and Genotype-Phenotype Correlations.

Hereditary thoracic aorta diseases (HTADs) are a heterogeneous group of rare disorders whose major manifestation is represented by aneurysm and/or dissection frequently located at the level of the ascending thoracic aorta. The diseases have an insidious evolution and can be encountered as an isolated manifestation or can also be associated with systemic, extra-aortic manifestations (syndromic HTADs). Along with the development of molecular testing technologies, important progress has been made in deciphering the heterogeneous etiology of HTADs. The aim of this study is to identify the genetic variants associated with a group of patients who presented clinical signs suggestive of a syndromic form of HTAD. Genetic testing based on next-generation sequencing (NGS) technology was performed using a gene panel (Illumina TruSight Cardio Sequencing Panel) or whole exome sequencing (WES). In the majority of cases (8/10), de novo mutations in the FBN1 gene were detected and correlated with the Marfan syndrome phenotype. In another case, a known mutation in the TGFBR2 gene associated with Loeys-Dietz syndrome was detected. Two other pathogenic heterozygous variants (one de novo and the other a known mutation) in the SLC2A10 gene (compound heterozygous genotype) were identified in a patient diagnosed with arterial tortuosity syndrome (ATORS). We presented the genotype-phenotype correlations, especially related to the clinical evolution, highlighting the particularities of each patient in a family context. We also emphasized the importance of genetic testing and patient monitoring to avoid acute aortic events.

The Importance of Molecular Genetic Testing for Precision Diagnostics, Management, and Genetic Counseling in MODY Patients.

Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic ß-cells. The diagnosis of MODY still remains a challenge for clinicians, with many cases being misdiagnosed as type 1 or type 2 diabetes mellitus (T1DM/T2DM), and over 80% of cases remaining undiagnosed. With the introduction of modern technologies, important progress has been made in deciphering the molecular mechanisms and heterogeneous etiology of MD, including MODY. The aim of our study was to identify genetic variants associated with MODY in a group of patients with early-onset diabetes/prediabetes in whom a form of MD was clinically suspected. Genetic testing, based on next-generation sequencing (NGS) technology, was carried out either in a targeted manner, using gene panels for monogenic diabetes, or by analyzing the entire exome (whole-exome sequencing). GKC-MODY 2 was the most frequently detected variant, but rare forms of KCNJ11-MODY 13, specifically, HNF4A-MODY 1, were also identified. We have emphasized the importance of genetic testing for early diagnosis, MODY subtype differentiation, and genetic counseling. We presented the genotype-phenotype correlations, especially related to the clinical evolution and personalized therapy, also emphasizing the particularities of each patient in the family context.

Advancing Cancer Research: Current Knowledge on Cutaneous Neoplasia.

Skin cancers require a multidisciplinary approach. The updated guidelines introduce new insights into the management of these diseases. Melanoma (MM), the third most common skin cancer, a malignant melanocytic tumor, which is classified into four major histological subtypes, continues to have the potential to be a lethal disease. The mortality-incidence ratio is higher in Eastern European countries compared to Western European countries, which shows the need for better prevention and early detection in Eastern European countries. Basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC) remain the top two skin cancers, and their incidence continues to grow. The gold standard in establishing the diagnosis and establishing the histopathological subtype in BCC and SCC is a skin biopsy. Sebaceous carcinoma (SeC) is an uncommon and potentially aggressive cutaneous malignancy showing sebaceous differentiation. It accounts for 0.7% of skin cancers and 3-6.7% of cancer-related deaths. Due to the rapid extension to the regional lymph nodes, SeC requires early treatment. The main treatment for sebaceous carcinoma is surgical treatment, including Mohs micrographic surgery, which has the advantage of complete margin evaluation and low recurrence rates. Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative diseases, with no evidence of extracutaneous determination at the moment of the diagnosis. PCLs have usually a very different evolution, prognosis, and treatment compared to the lymphomas that may secondarily involve the skin. The aim of our review is to summarize the important changes in the approach to treating melanoma, non-melanoma skin, cutaneous T and B cell lymphomas, and other types of skin cancers. For all skin cancers, optimal patient management requires a multidisciplinary approach including dermatology, medical oncology, and radiation oncology.

The Role of the Gut Microbiota in Anorexia Nervosa in Children and Adults-Systematic Review.

Among the factors incriminated in the appearance of eating disorders, intestinal microbiota has recently been implicated. Now there is evidence that the composition of gut microbiota is different in anorexia nervosa. We gathered many surveys on the changes in the profile of gut microbiota in patients with anorexia nervosa. This review comprehensively examines the contemporary experimental evidence concerning the bidirectional communication between gut microbiota and the brain. Drawing from recent breakthroughs in this area of research, we propose that the gut microbiota significantly contributes to the intricate interplay between the body and the brain, thereby contributing to overall healthy homeostasis while concurrently impacting disease risk, including anxiety and mood disorders. Particular attention is devoted to elucidating the structure and functional relevance of the gut microbiota in the context of Anorexia Nervosa.

Foreign Body Aspiration in Children-Retrospective Study and Management Novelties.

Foreign body aspiration (FBA) is a frequent diagnosis in children. In the absence of other lung conditions, such as asthma or chronic pulmonary infections, this manifests as a sudden onset of cough, dyspnea, and wheezing. The differential diagnosis is based on a scoring system which takes into account the clinical picture as well as the radiologic aspects. The treatment that is considered the gold-standard for FBA in children remains to be rigid fibronchoscopy, however it comes with several potentially crucial local complications such as airway edema, bleeding, and bronchospasm, along inherent issues due to general anesthesia. Material and methods: Our study is a retrospective study analyzing the medical files of the cases from our hospital over the span of 9 years. The study group consisted of 242 patients aged 0-16 years diagnosed with foreign body aspiration in the Emergency Clinical Hospital for Children "Sfânta Maria" Iași, between January 2010-January 2018. Clinical and imaging data were extracted from the patients' observation sheets. Results: In our cohort, the distribution of children with foreign body aspiration was uneven, with the highest incidence being reported in children from rural areas (70% of cases), whereas the most affected age group was 1-3 years, amounting to 79% of all cases. The main symptoms which led to emergency admittance were coughing (33%) and dyspnea (22%). The most important factors that determined the unequal distribution were socio-economic status, which relates to a lack of adequate supervision by parents, as well as the consumption of food inappropriate for their age. Conclusions: Foreign body aspiration is a major medical emergency that may be associated with dramatic clinical manifestations. Several scoring algorithms designed to establish the need for bronchoscopy have been proposed, taking into account both the clinical and radiological results. The issue with asymptomatic or mild symptomatic cases, as well as difficulties managing cases with radiolucent foreign bodies, remains a challenge.

The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine.

Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis.

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms.

Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs.

Social and Economic Determinants of Life Expectancy at Birth in Eastern Europe.

Life expectancy at birth is considered a parameter of the social development, health system, or economic development of a country. We aimed to investigate the effects of GDP per capita (as the economic factor), health care expenditure, the number of medical doctors (as social factors), and CO2 emissions (as the environmental factor) on life expectancy. We used panel data analysis for 13 Eastern European countries over the 2000-2020 period. After performing the analysis, we used a cross-country fixed-effects panel (GLS with SUR weights). According to our model, a one percent increase in health expenditure (as % of GDP) increases life expectancy at birth by 0.376 years, whereas each additional medical doctor per 10,000 inhabitants increases life expectancy at birth by 0.088 years on average. At the same time, each additional 10,000 USD per capita each year would increase life expectancy at birth by 1.8 years on average. If CO2 emissions increase by 1 metric ton per capita, life expectancy at birth would decrease by 0.24 years, suggesting that higher carbon emissions are capable of reducing longevity. Every European country has to make special efforts to increase the life expectancy of its inhabitants by applying economic and health policies focused on the well-being of the population.

Congenital Heart Malformations Masked by Infantile Gangliosidosis-Case Report and Growing Evidence for Metabolic Disease-Associated Aortopathies.

Gangliosidosis (ORPHA: 79255) is an autosomal recessive lysosomal storage disease (LSD) with a variable phenotype and an incidence of 1:200000 live births. The underlying genotype is comprised GLB1 mutations that lead to ß-galactosidase deficiency and subsequently to the accumulation of monosialotetrahexosylganglioside (GM1) in the brain and other organs. In total, two diseases have been linked to this gene mutation: Morquio type B and Gangliosidosis. The most frequent clinical manifestations include dysmorphic facial features, nervous and skeletal systems abnormalities, hepatosplenomegaly, and cardiomyopathies. The correct diagnosis of GM1 is a challenge due to the overlapping clinical manifestation between this disease and others, especially in infants. Therefore, in the current study we present the case of a 3-month-old male infant, admitted with signs and symptoms of respiratory distress alongside rapid progressive heart failure, with minimal neurologic and skeletal abnormalities, but with cardiovascular structural malformations. The atypical clinical presentation raised great difficulties for our diagnostic team. Unfortunately, the diagnostic of GM1 was made postmortem based on the DBS test and we were able to correlate the genotype with the unusual phenotypic findings.

Prenatal Diagnosis of Reno-Urinary Malformations in a Tertiary Center of Republic of Moldavia.

Malformative uropathy in children is one of the most common pathological conditions, with an incidence of 5-14% in newborns. Recent research shows that even in the current conditions, they are often diagnosed only in the advanced stages, when Chronic Kidney Disease is already affirming. This study's objective is to identify urinary tract anomalies, including malformative uropathies in the prenatal stage, using imaging techniques, namely ultrasound of the pregnant uterus. Using prenatal ultrasonography of the pregnant uterus and postnatal clinical and paraclinical examination, we prospectively evaluated a cohort of fifty children with pyelectasia. We describe the demographic and pathological characteristics of patients diagnosed with renal-urinary abnormalities, as well as their postnatal management. A prenatal diagnosis made during the first 15 to 22 weeks of pregnancy enables the evaluation of early malformative uropathies and the determination of the best time to operate in order to minimize complications. When prenatal ultrasonography, fetal karyotype, tissue sample, and embryonic appendages work together, problems may be partially or entirely revealed by these methods due to mistakes made in imaging examinations. In the case of a pregnancy with an antenatal malformation detected, it is necessary for the delivery to take place in a clinic that can provide favorable services for the survival and investigation of the child born with malformative abnormalities.

Obesity as a Risk Factor for the Severity of COVID-19 in Pediatric Patients: Possible Mechanisms-A Narrative Review.

Obesity, the current pandemic, is associated with alarming rises among children and adolescents, and the forecasts for the near future are worrying. The present paper aims to draw attention to the short-term effects of the excess adipose tissue in the presence of a viral infection, which can be life-threatening for pediatric patients, given that the course of viral infections is often severe, if not critical. The COVID-19 pandemic has been the basis of these statements, which opened the door to the study of the repercussions of obesity in the presence of a viral infection. Since 2003, with the discovery of SARS-CoV-1, interest in the study of coronaviruses has steadily increased, with a peak during the pandemic. Thus, obesity has been identified as an independent risk factor for COVID-19 infection and is correlated with a heightened risk of severe outcomes in pediatric patients. We sought to determine the main mechanisms through which obesity is responsible for the unfavorable evolution in the presence of a viral infection, with emphasis on the disease caused by SARS-CoV-2, in the hope that future studies will further elucidate this aspect, enabling prompt and effective intervention in obese patients with viral infections, whose clinical progression is likely to be favorable.

Diagnosis and Management of Simple and Complicated Meconium Ileus in Cystic Fibrosis, a Systematic Review.

The early management of neonates with meconium ileus (MI) and cystic fibrosis (CF) is highly variable across countries and is not standardized. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The protocol was registered in PROSPERO (CRD42024522838). Studies from three providers of academic search engines were checked for inclusion criteria, using the following search terms: meconium ileus AND cystic fibrosis OR mucoviscidosis. Regarding the patient population studied, the inclusion criteria were defined using our predefined PICOT framework: studies on neonates with simple or complicated meconium which were confirmed to have cystic fibrosis and were conservatively managed or surgically treated. Results: A total of 566 publications from the last 10 years were verified by the authors of this review to find the most recent and relevant data, and only 8 met the inclusion criteria. Prenatally diagnosed meconium pseudocysts, bowel dilation, and ascites on ultrasound are predictors of neonatal surgery and risk factor for negative 12-month clinical outcomes in MI-CF newborns. For simple MI, conservative treatment with hypertonic solutions enemas can be effective in more than 25% of cases. If repeated enemas fail to disimpact the bowels, the Bishop-Koop stoma is a safe option. No comprehensive research has been conducted so far to determine the ideal surgical protocol for complicated MI. We only found three studies that reported the types of stomas performed and another study comparing the outcomes of patients depending on the surgical management; the conclusions are contradictory especially since the number of cases analyzed in each study was small. Between 18% and 38% of patients with complicated MI will require reoperation for various complications and the mortality rate varies between 0% and 8%. Conclusion: This study reveals a lack of strong data to support management decisions, unequivocally shows that the care of infants with MI is not standardized, and suggests a great need for international collaborative studies.

Severe Liver Damage in an Obese Patient: Onset of Celiac Disease or Overlap Syndrome?

Celiac disease (CeD) is an enteropathy caused by the complex interaction between genetic, environmental, and individual immunological factors. Besides the hallmark of intestinal mucosal damage, CeD is a systemic disorder extending beyond the gastrointestinal tract and impacting various other organs, causing extraintestinal and atypical symptoms. The association between CeD and liver damage has been classified into three main categories: mild and asymptomatic liver injury, autoimmune liver injury, and liver failure. We present a case of severe liver damage with cirrhotic evolution in an obese 12-year-old boy who had been admitted due to generalized jaundice and localized abdominal pain in the right hypochondrium. In the course of investigating the etiology of severe liver disease, toxic, infectious, metabolic, obstructive, and genetic causes were excluded. Despite the patient's obesity, a diagnosis of CeD was established, and in accordance with autoimmune hepatitis (AIH) criteria, the patient was diagnosed with autoantibody-negative AIH associated to CeD.

Cardiotoxicity of Electronic Cigarettes and Heat-Not-Burn Tobacco Products-A Problem for the Modern Pediatric Cardiologist.

Electronic nicotine delivery systems (ENDS) have become increasingly popular among adolescents, either as an alternative to conventional cigarettes (CCs) or as a newly acquired recreational habit. Although considered by most users as a safer option for nicotine intake, these devices pose significant health risks, resulting in multisystem damage. Heat-not-burn products, which, unlike ENDS, contain tobacco, are also alternatives to CCs that consumers use based on the idea that their safety profile is superior to that of cigarettes. Recent studies in the USA and EU show that adolescents are particularly prone to using these devices. Pediatric cardiologists, as well as other healthcare professionals, should be aware of the complications that may arise from acute and chronic consumption of these substances, considering the cardiovascular damage they elicit. This article summarized the known data about the impact of ENDS on the cardiovascular system, with emphasis on the pathophysiological and molecular changes that herald the onset of systemic lesions alongside the clinical cardiovascular manifestations in this scenario.

Histopathological Images Analysis and Predictive Modeling Implemented in Digital Pathology-Current Affairs and Perspectives.

In modern clinical practice, digital pathology has an essential role, being a technological necessity for the activity in the pathological anatomy laboratories. The development of information technology has majorly facilitated the management of digital images and their sharing for clinical use; the methods to analyze digital histopathological images, based on artificial intelligence techniques and specific models, quantify the required information with significantly higher consistency and precision compared to that provided by optical microscopy. In parallel, the unprecedented advances in machine learning facilitate, through the synergy of artificial intelligence and digital pathology, the possibility of diagnosis based on image analysis, previously limited only to certain specialties. Therefore, the integration of digital images into the study of pathology, combined with advanced algorithms and computer-assisted diagnostic techniques, extends the boundaries of the pathologist's vision beyond the microscopic image and allows the specialist to use and integrate his knowledge and experience adequately. We conducted a search in PubMed on the topic of digital pathology and its applications, to quantify the current state of knowledge. We found that computer-aided image analysis has a superior potential to identify, extract and quantify features in more detail compared to the human pathologist's evaluating possibilities; it performs tasks that exceed its manual capacity, and can produce new diagnostic algorithms and prediction models applicable in translational research that are able to identify new characteristics of diseases based on changes at the cellular and molecular level.

Unexpected Dramatic Evolution of Placenta Increta: Case Report and Literature Review.

Placental morbid adherence is a known risk factor for postpartum hemorrhage. The incidence of abnormal placental attachment has been increasing over the past few decades, mainly due to rising rates of cesarean deliveries, advanced maternal age, and the use of assisted reproductive technologies. Cesarean section is a significant risk factor for placenta increta, as it disrupts the normal architecture of the uterine wall, making it more difficult for the placenta to detach after delivery. We present the case of a woman who underwent a cesarean section at 28 weeks due to anterior placenta previa, accompanied by hemorrhage and rupture of membranes. Following the delivery, she experienced normal postoperative bleeding and was discharged home after five days. However, six weeks later, she presented with heavy bleeding, leading to the decision to perform a total hysterectomy. The levels of HCG were found to be low. The pathological examination of the specimens confirmed a diagnosis of placenta increta, as it revealed notable placental proliferation, necrotic villi, and placental invasion near the uterine serosa. Notably, we did not find any similar cases documented in the literature. Patients experiencing prolonged vaginal bleeding after childbirth and diagnosed with placenta accreta should be closely monitored through ultrasound examinations; abnormal proliferation of the placenta can occur, and prompt detection is crucial for appropriate management.

Can Bioactive Food Substances Contribute to Cystic Fibrosis-Related Cardiovascular Disease Prevention?

Advances in cystic fibrosis (CF) care have significantly improved the quality of life and life expectancy of patients. Nutritional therapy based on a high-calorie, high-fat diet, antibiotics, as well as new therapies focused on CFTR modulators change the natural course of the disease. They do so by improving pulmonary function and growing BMI. However, the increased weight of such patients can lead to unwanted long-term cardiovascular effects. People with CF (pwCF) experience several cardiovascular risk factors. Such factors include a high-fat diet and increased dietary intake, altered lipid metabolism, a decrease in the level of fat-soluble antioxidants, heightened systemic inflammation, therapeutic interventions, and diabetes mellitus. PwCF must pay special attention to food and eating habits in order to maintain a nutritional status that is as close as possible to the proper physiological one. They also have to benefit from appropriate nutritional counseling, which is essential in the evolution and prognosis of the disease. Growing evidence collected in the last years shows that many bioactive food components, such as phytochemicals, polyunsaturated fatty acids, and antioxidants have favorable effects in the management of CF. An important positive effect is cardiovascular prevention. The possibility of preventing/reducing cardiovascular risk in CF patients enhances both quality of life and life expectancy in the long run.

Total Anomalous Pulmonary Venous Return in the Time of SARS-CoV-2-Case Report.

The management of children with complex and life-threatening heart malformations became a clinical conundrum during the SARS-CoV-2 pandemic. The pathophysiological features of the new coronavirus infection have raised major dilemmas regarding the postoperative evolution of an infected patient, and the epidemiological limitations have tightened the criteria for selecting cases. We present the case of a newborn diagnosed with total anomalous pulmonary venous return (TAPVR) who underwent surgical repair of the defect with favorable outcome, despite a prior diagnosis of SARS-CoV-2 infection. We discuss the medical and surgical management of TAPVR, highlighting possible management difficulties brought by the SARS-CoV-2 pandemic.

Nutritional Approach in Selected Inherited Metabolic Cardiac Disorders-A Concise Summary of Available Scientific Evidence.

Inborn errors of metabolism (IMDs) are a group of inherited diseases that manifest themselves through a myriad of signs and symptoms, including structural or functional cardiovascular damage. The therapy of these diseases is currently based on enzyme-replacement therapy, chaperone therapy or the administration of supplements and the establishment of personalized dietary plans. Starting from the major signs identified by the pediatric cardiologist that can indicate the presence of such a metabolic disease-cardiomyopathies, conduction disorders or valvular dysplasias-we tried to paint the portrait of dietary interventions that can improve the course of patients with mitochondrial diseases or lysosomal abnormalities. The choice of the two categories of inborn errors of metabolism is not accidental and reflects the experience and concern of the authors regarding the management of patients with such diagnoses. A ketogenic diet offers promising results in selected cases, although, to date, studies have failed to bring enough evidence to support generalized recommendations. Other diets have been successfully utilized in patients with IMDs, but their specific effect on the cardiac phenotype and function is not yet fully understood. Significant prospective studies are necessary in order to understand and establish which diet best suits every patient depending on the inherited metabolic disorder. The most suitable imagistic monitoring method for the impact of different diets on the cardiovascular system is still under debate, with no protocols yet available. Echocardiography is readily available in most hospital settings and brings important information regarding the impact of diets on the left ventricular parameters. Cardiac MRI (magnetic resonance imaging) could better characterize the cardiac tissue and bring forth both functional and structural information.

Atherosclerosis from Newborn to Adult-Epidemiology, Pathological Aspects, and Risk Factors.

Cardiovascular disease is the leading cause of mortality and morbidity throughout the world, accounting for 16.7 million deaths each year. The underlying pathological process for the majority of cardiovascular diseases is atherosclerosis, a slowly progressing, multifocal, chronic, immune-inflammatory disease that involves the intima of large and medium-sized arteries. The process of atherosclerosis begins in childhood as fatty streaks-an accumulation of lipids, inflammatory cells, and smooth muscle cells in the arterial wall. Over time, a more complex lesion develops into an atheroma and characteristic fibrous plaques. Atherosclerosis alone is rarely fatal; it is the further changes that render fibrous plaques vulnerable to rupture; plaque rupture represents the most common cause of coronary thrombosis. The prevalence of atherosclerosis is increasing worldwide and more than 50% of people with circulatory disease die of it, mostly in modern societies. Epidemiological studies have revealed several environmental and genetic risk factors that are associated with the early formation of a pathogenic foundation for atherosclerosis, such as dyslipidemia, hypertension, diabetes mellitus, obesity, and smoking. The purpose of this review is to bring together the current information concerning the origin and progression of atherosclerosis in childhood as well as the identification of known risk factors for atherosclerotic cardiovascular disease in children.