Pediatrics of disability: a comprehensive approach to the child with syndromic psychomotor delay

: Intellectual disability is the impairment of cognitive, linguistic, motor and social skills that contribute to the global level of intelligence that occurs in the pediatric age, and now comprises also the term “mental retardation” used in the past to describe the same impairments under 5 years of age. Intellectual disability involves 3% of the general population, also due to a genetic cause including chromosome aberrations to account for the 3–28% of intellectual disability. Between people with intellectual disabilities, the cause of the disorders was identified as a single gene disorder up to 12%, as multifactorial disorders up to 4%, and as genetic disorders up to 8.5%. Children affected by a malformation syndrome associated with mental retardation or intellectual disability represent a care challenge for the pediatrician. The presence of a multidisciplinary team is essential to manage the patient, trying to control the complications of the syndrome for promoting the correct psychophysical development. This encourages continuous follow-up of these children since the pediatrician is essential both in the clinical management of the syndrome and in facilitating the social integration of these children.

Personalized Medicine in Autoimmune Diseases

Autoimmune diseases are multifactorial disorders caused by both genetic and environmental factors and without a known cure [...]

Le interferonopatie di tipo I

Type I interferonopathies are autoinflammatory monogenic disorders arising from excessive production of interferons. Some manifestations like chilblains, neurologic involvement, arthritis and lipodystrophy may be shared by several diseases. Measure of interferon score and genetic analysis can assist a definite diagnosis. Among immunomodulant drugs, glucocorticoids, micofenolate and antimalarials can be of some benefit, however other drugs like JAK inhibitors seem more effective in controlling interferon-related complaints. Apart from allowing better diagnosis and care to affected patients, the study of interferonopathies may also reflect on a better knowledge on multifactorial disorders associated with interferon-related inflammation.

Sensogenomics and the Biological Background Underlying Musical Stimuli: Perspectives for a New Era of Musical Research

What is the actual impact of music on the human being and the scope for scientific research in this realm? Compared to other areas, the study of the relationship between music and human biology has received limited attention. At the same time, evidence of music’s value in clinical science, neuroscience, and social science keeps increasing. This review article synthesizes the existing knowledge of genetics related to music. While the success of genomics has been demonstrated in medical research, with thousands of genes that cause inherited diseases or a predisposition to multifactorial disorders identified, much less attention has been paid to other human traits. We argue for the development of a new discipline, sensogenomics, aimed at investigating the impact of the sensorial input on gene expression and taking advantage of new, discovery-based ‘omic’ approaches that allow for the exploration of the whole transcriptome of individuals under controlled experiments and circumstances.

Evaluation of population frequency for age-dependent multifactorial disorders

Aim. Description of the method to calculate the population incidence of age- and sex-dependent multifactorial diseases. Methods. For the analysis, we used statistical material of psychiatric hospitals in the Kharkiv region for 2016. Calculation of the population frequency was carrying out according to the methodology used in demographic studies. Results. In medical genetics, population frequency is mainly used for prognostic purposes to assess the genetic load of a population or to calculate the probability to inherit a disease. Evaluation of the population frequency of multifactorial disease is complicated by varying age of onset, differential survival, different thresholds of hereditary predisposition for men and women. Prevalence, which is often used instead population frequency, is not a gene pool characteristic and is not useful for genetic analysis and risk assessment. The population frequency, calculated for affective disorders by the proposed method (0.184%), is 1.33 times higher than the prevalence rate (0.138%), that is, a third of cases when using the prevalence turns out to be lost that distorts the derived genetic indicators. Conclusions. For the correct evaluation of the population frequency, the age-specific incidence for two sexes separately must be estimated, followed by the calculation of the cumulative frequencies. Keywords: multifactorial diseases, prevalence, morbidity, population frequency.

The role of family history as a risk factor for non-syndromic cleft lip and/or palate with multifactorial inheritance

Background: Cleft lip with or without cleft palate (CL/P) is a facial growth ‘disorder that occurs during gestation and has multifactorial causes owing to both genetic and environmental factors. Several factors can increase the likelihood of CL/P, and one of them is family history. Differences in results obtained from studies conducted across several countries concerning family history as a risk factor for CL/P suggest there is no consensus on how the condition is inherited. Purpose: This study aims to review the literature on the role of family history as a risk factor contributing to the incidence of non-syndromic CL/P (NSCL/P). Review: This review discusses the etiology of CL/P and the risk factors influencing the incidence of CL/P. The review also examines the criteria for inheriting multifactorial disorders to calculate the risks involved should there be a recurrence of the condition based on family history. Conclusion: CL/P is a type of multifactorial disorder with unclear etiology. Therefore, it is important to investigate the risk factors stemming from family history (which play an important role) related to the recurrence risk. Additionally, there should be focus on increasing genetic education and offering counselling to parents and pregnant women.

Vasculitis, Autoimmunity, and Cytokines: How the Immune System Can Harm the Brain

More and more findings suggest that neurological disorders could have an immunopathological cause. Thus, immune-targeted therapies are increasingly proposed in neurology (even if often controversial), as anakinra, inhibiting IL-1 for febrile inflammatory illnesses, and JAK inhibitors for anti-interferons treatment. Precision medicine in neurology could be fostered by a better understanding of the disease machinery, to develop a rational use of immuno-modulators in clinical trials. In this review, we focus on monogenic disorders with neurological hyper-inflammation/autoimmunity as simplified “models” to correlate immune pathology and targeted treatments. The study of monogenic models yields great advantages for the elucidation of the pathogenic mechanisms that can be reproduced in cellular/animal models, overcoming the limitations of biological samples to study. Moreover, monogenic disorders provide a unique tool to study the mechanisms of neuroinflammatory and autoimmune brain damage, in all their manifestations. The insight of clinical, pathological, and therapeutic aspects of the considered monogenic models can impact knowledge about brain inflammation and can provide useful hints to better understand and cure some neurologic multifactorial disorders.

Influence of Materials Properties on Bio-Physical Features and Effectiveness of 3D-Scaffolds for Periodontal Regeneration

Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can lead to the detachment of gum from teeth, causing their loss. To date it is estimated that severe periodontal diseases affect around 10% of the population worldwide thus making necessary the development of effective treatments able to both reduce the infections and inflammation in injured sites and improve the regeneration of damaged tissues. In this scenario, the use of 3D scaffolds can play a pivotal role by providing an effective platform for drugs, nanosystems, growth factors, stem cells, etc., improving the effectiveness of therapies and reducing their systemic side effects. The aim of this review is to describe the recent progress in periodontal regeneration, highlighting the influence of materials’ properties used to realize three-dimensional (3D)-scaffolds, their bio-physical characteristics and their ability to provide a biocompatible platform able to embed nanosystems.

Methylenetetrahydrofolate reductase gene rs1801133 polymorphism and essential hypertension risk from a comprehensive analysis

Background Essential hypertension (EH) is common and multifactorial disorders likely to be influenced by multiple genes. The methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 polymorphism is related to MTHFR enzyme activity and to plasma homocysteine concentration. In addition, variations in MTHFR functions likely play roles in the etiology of EH. So far, larger number of studies between MTHFR rs1801133 polymorphism and EH have provided controversial or inconclusive results. To better assess the purported relationship, we performed a comprehensive analysis of 50 publications. Methods Eligible studies were identified by searching the PubMed, Wanfang and CNKI databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess this association. Results Overall, increased significant associations were detected between MTHFR rs1801133 polymorphism and EH risk (such as T vs. C: OR = 1.37, 95%CI = 1.24–1.52, P = 0.000), the same as in race subgroup (Asian: T vs. C: OR = 1.46, 95%CI = 1.29–1.67, P = 0.000; China: T vs. C: OR = 1.51, 95%CI = 1.30–1.74, P = 0.000). Similar associations were also found in source of control and genotype methods subgroups. Conclusions Our study showed evidence that MTHFR rs1801133 null genotype may increase EH risk. Future studies with larger sample size are warranted to further evaluate this association in more detail.

Uromodulin: Roles in Health and Disease

Uromodulin, a protein exclusively produced by the kidney, is the most abundant urinary protein in physiological conditions. Already described several decades ago, uromodulin has gained the spotlight in recent years, since the discovery that mutations in its encoding gene UMOD cause a renal Mendelian disease (autosomal dominant tubulointerstitial kidney disease) and that common polymorphisms are associated with multifactorial disorders, such as chronic kidney disease, hypertension, and cardiovascular diseases. Moreover, variations in uromodulin levels in urine and/or blood reflect kidney functioning mass and are of prognostic value for renal function, cardiovascular events, and overall mortality. The clinical relevance of uromodulin reflects its multifunctional nature, playing a role in renal ion transport and immunomodulation, in protection against urinary tract infections and renal stones, and possibly as a systemic antioxidant. Here, we discuss the multifaceted roles of this protein in kidney physiology and its translational relevance.