Macrocephaly and Finger Changes: A Narrative Review.

Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.

The evaluation of heavy metals in transylvania, as predictor for the health status of the exposed population.

It is well known and proven that heavy metal contamination of the soils can severely affect the health of the people living in the contaminated areas given the ease with which trace elements can enter the human body. In addition-to agricultural crop depreciation as well as soil erosion, soil pollution can negatively affect the natural function of ecosystems. While certain heavy metals in high doses can be harmful to the body, others such as cadmium, mercury, lead, chromium, silver and arsenic in minimal amounts have delusional effects on the body, causing acute and chronic intoxication. Our research is focused on the identification of heavy metals from the soil (O, Al, Ca, Cu, Fe, K, Mg, Na, P, Pb, Si, Ti, Zn) in 3 areas in Transylvania where factories were in operation, using 4 methods: UV-VIS spectrometry, AAS, SEM-EDAX and X-ray diffractions. High levels of very toxic trace elements such as lead, aluminum, cadmium were found near the studied areas, especially using SEM-EDAX and AAS methods. Knowledge on the soil concentration of TEs, the time exposure and the side effects can lead us to predict the health status of the exposed population. In our study, by determinating the concentration of TEs we set out to formulate a prediction on the health status of the exposed population using literature data.

Actual Weight, Perceived Weight and Desired Weight of Romanian School Children by Parents and Children.

Background and Objectives: The perception of the body weight by children and parents influences the consequent actions undertaken for children's body weight management. This study investigated the correspondence between objective evaluations of Romanian school children (actual weight) and perceptions about weight (perceived weight), preoccupation with body weight management (desired weight) and parents' perceptions on children's weight. Materials and Methods: A cross sectional study was performed among 344 children aged 11 to 14 and 147 parents from Cluj-Napoca, Romania. We made anthropometric measurements of children, and short questionnaires were completed by the children and the parents. Results: The results show that 3.8% of children were underweight, 68.3% had a normal weight and 27.9% were overweight. Of this sample, 61.5% of underweight children, 20% of normal weight children and 43.7% of overweight children had misperceptions about their weight. The percentage of parents who did not estimate their children's weight correctly was 50%, 11.9% and 41.5%, respectively, for each of the three weight groups. The results of the logistic regression analyses showed that several factors were associated with the misclassification of their own body weight by the children, such as body mass index, gender, weight management practices, misclassification by the parents as well as parent-child discussions on these issues. Conclusions: Education for both Romanian parents and children is needed with regard to correctly identifying and managing children' body weight.

Genetic and Environmental Factors in the Pathophysiology of Hashimoto's Thyroiditis.

Finding multiple familial patients with Hashimoto thyroiditis in our clinic a search in the literature confirms that genetic factors, in addition to environmental factors, seem involved in the etiology of this disease.

Exploring Cardiovascular Involvement in Tuberous Sclerosis: Insights for Pediatric Clinicians.

Tuberous sclerosis is a rare genetic disorder involving mainly the nervous and cardiovascular systems. The early recognition of the cardiovascular manifestations by the pediatrician allows an appropriate management and therefore enhances the quality of life of the affected children. Cardiac rhabdomyomas and the associated arrhythmias are the first cardiac features and they might represent a diagnosis challenge given their wide spectrum of clinical manifestations. We aimed to provide the paediatric practitioners with current knowledge regarding the cardiovascular complications in children with tuberous sclerosis. We overviewed the antenatal and postnatal evolution of cardiovascular manifestations, the systematic screening and long-term follow-up strategy of cardiac rhabdomyomas and arrhythmias in children with tuberous sclerosis.

A Pilot Study of Multiplex Ligation-Dependent Probe Amplification Evaluation of Copy Number Variations in Romanian Children with Congenital Heart Defects.

Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10-15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4, TBX5, NKX2-5, BMP4, and CRELD1 genes in patients with syndromic and isolated CHDs. A total of 56 patients were included in the study, half of them (28 subjects) being classified as syndromic. The most common heart defect in our study population was ventricular septal defect (VSD) at 39.28%. There were no statistically significant differences between the two groups in terms of CHD-type distribution, demographical, and clinical features, with the exceptions of birth length, weight, and length at the time of blood sampling, that were significantly lower in the syndromic group. Through multiplex ligation-dependent probe amplification (MLPA) analysis, we found two heterozygous deletions in the 22q11.2 region, both in patients from the syndromic group. No CNVs involving GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes were identified in our study. We conclude that the MLPA assay may be used as a first genetic test in patients with syndromic CHD and that the 22q11.2 region may be included in the panels used for screening these patients.

Genetic Alterations of Transcription Factors and Signaling Molecules Involved in the Development of Congenital Heart Defects-A Narrative Review.

Congenital heart defects (CHD) are the most common congenital abnormality, with an overall global birth prevalence of 9.41 per 1000 live births. The etiology of CHDs is complex and still poorly understood. Environmental factors account for about 10% of all cases, while the rest are likely explained by a genetic component that is still under intense research. Transcription factors and signaling molecules are promising candidates for studies regarding the genetic burden of CHDs. The present narrative review provides an overview of the current knowledge regarding some of the genetic mechanisms involved in the embryological development of the cardiovascular system. In addition, we reviewed the association between the genetic variation in transcription factors and signaling molecules involved in heart development, including TBX5, GATA4, NKX2-5 and CRELD1, and congenital heart defects, providing insight into the complex pathogenesis of this heterogeneous group of diseases. Further research is needed in order to uncover their downstream targets and the complex network of interactions with non-genetic risk factors for a better molecular-phenotype correlation.

Body size influences heart rate in children aged 6 to 18 years old.

Previous research established age-related normal limits for children's heart rates (HRs). However, children of the same age can have significantly different HRs, depending on whether they are overweight or underweight, tall or short. Studies on children HR have failed to find a clear correlation between HR and body size. The goal of our study was to create Z scores for HR based on weight (W), height (H), body mass index (BMI), and body surface area (BSA) and compare them to normal age-related HR limits. Electrocardiograms were recorded from a total of 22,460 healthy children ranging in age from 6 to 18 years old using BTL machines. A comparison was made between different age groups, in function of W, H, BMI, and BSA, based on the HR that was automatically detected by using the digitally stored electrocardiogram. Z scores were computed for each of the categories that were mentioned. Incremental Z score values between -2.5 and 2.5 were calculated to establish upper and lower limits of HR. The BSA's estimation of HR is the most accurate of the available methods and can be utilized with accuracy in clinical practice. Z scores for HR in children differ in function of the age, W, H, BMI and BSA. The best estimation is based on BSA. The novelty of our study is that we developed Z scores for HR in relation to body size, age and sex, producing a standardized, consistent, and reproducible result without requiring practitioners to learn and remember cutoff values for a wide range of variables across age groups and sexes. Z scores minimize observer and institutional bias, hence generating uniform and reproducible standards.

PFAPA Syndrome: Clinical, Laboratory and Therapeutic Features in a Single-Centre Cohort.

Objective: The aim of this study is to describe a group of Romanian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. Materials: This consisted of 39 children diagnosed with PFAPA syndrome according to Thomas' criteria (eight patients with an age at diagnosis <1 year and 31 patients with an age at diagnosis >1 year). Methods: Retrospective analysis of the patients with PFAPA syndrome was focused on clinical features, laboratory findings and therapeutic methods. Comparison between the two groups divided by age at onset was also investigated. Results: Median age at onset was 1.58 years, and median age at diagnosis was 2.97 years. The mean interval between episodes was 35.5 days and the mean duration per febrile episode was 4.1 days. The median diagnosis delay was 2.42 years. The patients presented pharyngitis (100%), adenitis (94.8%) and aphthous lesions (66.7%). The frequency of febrile attacks was higher in children with an age at diagnosis under 1 year (p = 0.0287). Younger age was associated with the presence of aphthae. The mean value of C-reactive protein (CRP) was 7.9mg/dl and the mean value of leucocytes was 14,839/mm3. In 95% of patients given oral corticosteroids, remission of symptoms was reported within 24 h. In three patients, tonsillectomy was performed with complete remission of the disease. Conclusion: We present a cohort of children with PFAPA syndrome, with clinical and laboratory features similar to those described in the literature. Febrile attacks had a higher incidence in children with younger age at the onset of the disease. The patients had a favorable response to corticosteroids.

Diagnosis and Management of Genetic Causes of Middle Aortic Syndrome in Children: A Comprehensive Literature Review.

Middle aortic syndrome (MAS) is a rare vascular disease representing an important cause of severe hypertension in children. MAS is characterized by segmental or diffuse narrowing of the abdominal and/or distal descending aorta with involvement of the renal and visceral branches. Most cases of MAS are idiopathic, but MAS may occur in genetic and acquired disorders. The most common genetic causes of MAS are neurofibromatosis type I, Williams syndrome, Alagille syndrome, tuberous sclerosis and mucopolysaccharidosis. This review article discusses the pathophysiological aspects, distinctive associated features, and management of genetic forms of MAS in children.

Evaluation of Circulating Chitotriosidase Activity in Children with Obesity.

Childhood obesity progresses to metabolic disturbances via low-grade inflammation. Identifying novel molecules that reflect the activity of the immune responses is critical in understanding its underlying pathogenesis. Our exploratory study aimed to evaluate the change of chitotriosidase (CHIT1) plasma activity according to Body Mass Index (BMI)-for-age z score in pediatric patients. The study evaluated 68 children consisting of 47.1% girls with a mean age of 12.47 ± 3.71 years and 52.9% boys with a mean age of 11.93 ± 3.18 years. The effect of the most frequent CHIT1 gene variants, the 24 base pair duplication (dup24) and G102S polymorphism, upon the association between circulating CHIT1 activity and the obesity level, was also investigated. A significantly higher logCHIT1 plasma activity was found in children with extreme obesity than in children with overweight (p = 0.048 for the uncorrected CHIT1 and 0.026 for the corrected CHIT1). The BMI-for-age z score significantly (p = 0.031) predicts increased CHIT1 activity in children with overweight, obesity, and extreme obesity after controlling for the two gene variants, age, gender, and time since weight gain. Dup24 and G102S polymorphism were significant independent predictors (p-values < 0.002) for the change of CHIT1 plasma activity. Circulating CHIT1 might be an accurate indicator of inflammation in children with obesity. Its role and the effect of the dup24 and G102S variants on the CHIT1 activity should be validated in a larger cohort.

Anatomical-MRI Correlations in Adults and Children with Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is the most frequent hereditary cardiovascular disease and the leading cause of sudden cardiac death in young individuals. Advancements in CMR imaging have allowed for earlier identification and more accurate prognosis of HCM. Interventions aimed at slowing or stopping the disease's natural course may be developed in the future. CMR has been validated as a technique with high sensitivity and specificity, very few contraindications, a low risk of side effects, and is overall a good tool to be employed in the management of HCM patients. The goal of this review is to evaluate the magnetic resonance features of HCM, starting with distinct phenotypic variants of the disease and progressing to differential diagnoses of athlete's heart, hypertension, and infiltrative cardiomyopathies. HCM in children has its own section in this review, with possible risk factors that are distinct from those in adults; delayed enhancement in children may play a role in risk stratification in HCM. Finally, a number of teaching points for general cardiologists who recommend CMR for patients with HCM will be presented.

Low Atrial Rhythm in a Large Cohort of Children from Transylvania, Romania.

Low atrial rhythm (LAR) is an ectopic rhythm originating in the lower part of the right or left atrium. Prior observational studies attempted to quantify the prevalence of low atrial rhythm in the pediatric population, but the observed prevalence was highly variable with relatively small sample sizes. We aimed to characterize low atrial rhythm and determine its prevalence in a large population of 24,316 asymptomatic children from northwestern Transylvania. We found a prevalence of 0.6% (145 children) for low atrial rhythm. Children with LAR had a significantly lower heart rate (mean 78.6 ± 8.3 bpm), than the control sinus rhythm group (85.02 ± 4.5 bpm). Furthermore, a shorter PR interval was seen in children with LAR (132.7 ± 12.7 ms) than in the children from the control group (141.7 ± 5.4; p = 0.0001).There was no significant association between gender and the presence of left LAR (LLAR) or right LAR (RLAR) (p = 0.5876). The heart rate of children with LLAR was significantly higher (81.7 ± 11.6 bpm) than that of the children with LRAR (77.6 ± 11.1 bpm) (p = 0.037). Pediatric cardiologists should recognize low atrial rhythm and be aware that asymptomatic, healthy children can exhibit this pattern, which does not require therapeutic intervention.

One Molecule for Mental Nourishment and More: Glucose Transporter Type 1-Biology and Deficiency Syndrome.

Glucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the SLC2A1 gene, impairing passive glucose transport across the blood-brain barrier. All age groups, from infants to adults, may be affected, with age-specific symptoms. In its classic form, the syndrome presents as an early-onset drug-resistant metabolic epileptic encephalopathy with a complex movement disorder and developmental delay. In later-onset forms, complex motor disorder predominates, with dystonia, ataxia, chorea or spasticity, often triggered by fasting. Diagnosis is confirmed by hypoglycorrhachia (below 45 mg/dL) with normal blood glucose, 18F-fluorodeoxyglucose positron emission tomography, and genetic analysis showing pathogenic SLC2A1 variants. There are also ongoing positive studies on erythrocytes' Glut1 surface expression using flow cytometry. The standard treatment still consists of ketogenic therapies supplying ketones as alternative brain fuel. Anaplerotic substances may provide alternative energy sources. Understanding the complex interactions of Glut1 with other tissues, its signaling function for brain angiogenesis and gliosis, and the complex regulation of glucose transportation, including compensatory mechanisms in different tissues, will hopefully advance therapy. Ongoing research for future interventions is focusing on small molecules to restore Glut1, metabolic stimulation, and SLC2A1 transfer strategies. Newborn screening, early identification and treatment could minimize the neurodevelopmental disease consequences. Furthermore, understanding Glut1 relative deficiency or inhibition in inflammation, neurodegenerative disorders, and viral infections including COVID-19 and other settings could provide clues for future therapeutic approaches.

ROHHAD (Rapid-onset Obesity with Hypoventilation, Hypothalamic Dysfunction, Autonomic Dysregulation) Syndrome-What Every Pediatrician Should Know About the Etiopathogenesis, Diagnosis and Treatment: A Review.

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) syndrome is a rare disease with unknown and debated etiology, characterized by precipitous obesity in young children, hypoventilation and autonomic dysregulation with various endocrine abnormalities. Neuroendocrine tumors can be associated in more than half of the cases. This rare condition has a severe outcome because of high morbidity and mortality. We provide a comprehensive description of the etiopathogenetic theories of the disease, clinical presentation, diagnostic workup and treatment possibilities.

Inflammation-Related Markers and Thyroid Function Measures in Pediatric Patients: Is the Grade of Obesity Relevant?

We aimed to investigate the effect of weight status on inflammation-related markers and thyroid function tests in overweight and obese pediatric patients. Children and adolescents diagnosed between January 2017 and January 2019 with overweight or obesity were included in the study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated for the groups defined according to Body Mass Index (BMI)-for-age z-score: overweight (≥1 BMI-for-age z-score), obese (≥2 BMI-for-age z-score) and severely obese (≥3 BMI-for-age z-score). Severely obese patients had significantly higher value of white blood cells (WBC) counts (median = 7.92) compared with overweight patients (7.37, p = 0.014). Absolute lymphocyte count was significantly associated with obesity degree in children (Spearman's Rho coefficient ρ = 0.228. p = 0.035), whereas absolute polymorphonuclear neutrophils (PMNCs) count was significantly higher in severely obese adolescents than overweight adolescents (overweight: 4.04 vs. severely obese: 5.3 (p = 0.029)). In 8.19% of patients an elevated thyroid-stimulating hormone (TSH) level was found, and 3.36% of patients had a low level of free thyroxine with an elevated level of TSH. Total absolute WBC count may be a reliable inflammation-related marker in obese pediatric patients without metabolic syndrome, but needs to be validated in the context of all possible covariates. Subclinical and overt hypothyroidism may develop from an early age in overweight or obese patients.

Early clinical signs in lysosomal diseases.

BACKGROUND AND AIM: The lysosomal storage diseases are a group of monogenic diseases with multisystemic impairment and chronic progression induced by the deficiency of lysosomal acid hydrolases involved in the breakdown of various macromolecules. The accumulation occurs in the macrophages of the reticule-endothelial system and causes enlargement and functional impairment. The mainly involved organs are the brain, liver, spleen, bones, joints, airways, lungs, and heart. The aim of this study was to evaluate early symptoms, signs and the delay in the diagnosis of different lysosomal diseases. METHODS: The medical documentation of 188 patients with lysosomal storage disorders, aged 1-70 years, were analyzed. All these patients were specifically diagnosed, by enzyme and molecular assay. RESULTS: The age of clinical signs onset varies in different type of lysosomal diseases, from the first months of life or early childhood in severe form, to adulthood in attenuated forms. The delay between the clinical signs onset and specific diagnosis ranged from 0.5 months to 57.91 years. CONCLUSIONS: The lysosomal storage diseases are rare diseases with childhood onset, but these early signs and symptoms are not recognized and are often taken into account when the vital organs damage becomes manifest.

Validation of Normal P-Wave Parameters in a Large Unselected Pediatric Population of North-Western Romania: Results of the CARDIOPED Project.

AIMS: Reference values of the P-wave on 12 lead electrocardiograms are lacking for children and adolescents in Eastern Europe. Hence, the present study is aimed at determining the standard values of the P-wave in children and adolescents based on ECG data from the CARDIOPED project, a large-scale general population of children who participated in a screening program in Transylvania, Romania. METHODS AND RESULTS: A total of 22,411 ECGs of participants aged 6 to 18 years old from a school-based ECG screening were obtained between February 2015 and December 2015 in Transylvania, Romania. Three pediatric cardiologists manually reviewed each ECG. P-wave duration, voltage, axis, and correlation with gender and age were analyzed. The mean P-wave duration was 88 ± 10.7 ms, with a maximum duration of 128 ms. P-wave showed a positive correlation with age but did not differ between sexes. There was a positive correlation between the P-wave duration and the heart rate, but not with the body max index. The mean P-wave axis was 40.4 ± 31.1, and the mean P-wave amplitude was 0.12 ± 0.03 mV. CONCLUSION: In this study on many pediatric subjects, we have provided normal limits for the P-wave in Romanian children aged 6-18 years. Our findings are useful for creating interpretation guidelines for pediatric ECG.

Prevalence of Underweight, Overweight and Obesity in School-Aged Children in the Urban Area of the Northwestern Part of Romania.

INTRODUCTION: During the last three decades, there has been an excess weight epidemic due to changes in nutrition and lifestyle. Few data on the prevalence of overweight and obesity in children in Romania were published, without a single study representative at the national level. There are reports on the higher level of overweight and obesity in urban areas compared to rural ones. This study aimed to estimate the prevalence of underweight, overweight, obesity and severe obesity in children enrolled in schools from the urban area. MATERIAL AND METHODS: For this cross-sectional study, children from 177 schools from the urban area of five counties from the northwestern part of Romania were included after the parents signed written informed consent. Anthropometric data were recorded (weight, height) based on World Health Organization (WHO) recommendations and Body-Mass-Index (BMI), and the z-score for BMI were calculated. The nutritional status was estimated using three reference criteria: WHO, International Obesity Task Force (IOTC) and the Center for Disease Control and Prevention (CDC). RESULTS: We analyzed data of 21,650 children (48.19% boys) age between 7 and 18 years. The prevalence of overweight was 13.8%, 16.2% and 20.3%, of obesity was 10.7%, 10.0% and 5.7% and of severe obesity was 5.1%, 1.2% and 1.6% (using WHO, CDC and IOTF cut-offs). Underweight was present in 5.2% (WHO), 6% (CDC) and 2.6% (IOTF). The highest prevalence of overweight (including obesity) was found in children aged 10 years, and the lowest in adolescents at 18 years. Boys have a higher prevalence of excess weight than girls. Using IOTF cut-offs, the prevalence of obesity and severe obesity was lower than using WHO criteria. CONCLUSIONS: The prevalence of overweight (including obesity) in children from the urban area of Western Romania was recorded at alarming levels, higher in boys and at the pre-puberty ages. There are significant differences based on the reference system used. It is important to correctly choose the reference for the definition of overweight and obesity to have the correct estimation of the target for public health measures.

Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects.

Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient's life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.