Hereditary Pathology Research Articles

Система контроля качества и безопасности оказания медицинской помощи как один из ключевых элементов достижения целей расширенного неонатального скрининга в Российской Федерации

After analyzing the Russia-wide Extended neonatal screening (ENS) system for hereditary and/or congenital diseases results it became necessary to change the ENS tasks ranking: the highest priority among them as yet is an increase in the congenital and/or hereditary diseases detection level and a decrease in the therapy initiation age. The results of an on-site audit conducted in 20 Russia regions in 2024 showed significant differences from the target indicators that in its turn had made it possible to determine the control points and roadmap operational procedures as necessary elements for the ENS system improvement with the purpose of medical care quality and safety monitoring in order to increase the congenital and/or hereditary pathology detection level, to reduce the time span from birth to the therapy initiation and to increase the effectiveness of patient treatment.

Prolonged catamnesis of a child with type I mucopolysaccharidosis, Gurler syndrome, receiving enzyme replacement therapy

Hereditary pathology makes up a significant part of the structure of childhood morbidity, disability and mortality. Mucopolysaccharidosis type I is a hereditary lysosomal accumulation disease, with an autosomal recessive type of inheritance. At birth, children with Gurler syndrome look normal, but in the future, they develop symptoms characteristic of mucopolysaccharidosis, and the first clinical manifestations of the disease are often hernias and hepatosplenomegaly. The presented clinical case demonstrates the difficulties of early diagnosis of mucopolysaccharidosis type I, which lead to a later prescription of enzyme replacement therapy and the inability to use a more effective method of therapy – hematopoietic stem cell transplantation, due to the development of serious manifestations of the cardiovascular system. While the positive effects of enzyme replacement therapy in the early stages of treatment may seem promising, it does not guarantee a favorable prognosis for the future.Conclusion. Currently, early diagnosis of mucopolysaccharidosis type I is difficult due to the lack of early manifestations. Often, the progression of clinical manifestations leads to disability, and in severe cases, to death. Therefore, it is important to have early diagnosis and appropriate treatment.

Drug-resistant epilepsy cases in chromosomal pathology

Two cases of epilepsy in patients with a rare hereditary pathology associated with a chromosomal mutation caused deletion of chromosome 14 are presented. In the first case, this pathology was manifested in the child by generalized tonic-clonic seizures, delayed psycho-verbal development, and facial skull microanomaly. In the second case, it was expressed in tonic epileptic seizures, delayed psycho-verbal development, developmental microanomalies, pyramidal atactic syndrome and hand joint hypermobility. Such clinical observations are of professional and scientific interest, as they relate to a rare neurological pathology, with drug-resistant epilepsy as a leading sign.

Mucopolysaccharidosis Type I (Hurler – Scheie Syndrome): Case Report

Background. Mucopolysaccharidosis type I (MPS I) is an inherited disease caused by pathogenic variants in the IDUA gene, which encodes the lysosomal enzyme alpha-L-iduronidase. This clinical case demonstrates the importance of diagnosing rare diseases when patients have phenotypic features indicating hereditary pathology presence. Phenotype changes can be so-called “red flag” that helps specialists suspect and diagnose lysosomal storage diseases. Clinical case description. The patient was observed with delayed psychomotor development; she also had hepatomegaly and on auscultation of the heart there was a functional systolic murmur above the apex and in the Botkin–Erb point on heart auscultation. Coarse “garholoid” facial features attracted attention at external examination: large nose, wide sunken nose bridge, macroglossia, thick lips, synophrysis, scaphocephaly, wide chest, and flat-valgus feet. Echocardiography has revealed mitral valve insufficiency and hardened valve leaflets. Ophthalmologist examination: hypermetropic astigmatism. Psychiatrist examination: mental and speech development delay. Enzymatic diagnostics: significant decrease in alpha-Liduronidase activity. No further examinations were carried out due to the onset of the COVID-19 epidemic and parents' doubts about the diagnosis. The patient was readmitted to the hospital at the age of 6 years due to aggravation of her condition. A molecular genetic study has revealed two pathogenic variants in the IDUA gene. Diagnosis of MPS I was established according to the clinical data, results of biochemical and molecular genetic studies. Conclusion. This clinical case demonstrates the classic course of MPS I with typical phenotypic signs and lesions in various organs and systems. The presented case demonstrates the importance of professional vigilance among doctors of various specialties regarding orphan diseases.

Neurodevelopmental Disorders in Children with Hereditary Diseases (Review of Literature, Clinical Case Report)

Introduction. The majority of studies on disturbed neurodevelopment in children focus on psychiatric or psychological-pedagogical issues, but the genetic component of pathology also occupies an important place, in which is important to conduct genetic investigation to verify hereditary pathology, and to identify target organs inherent in particular hereditary disease. The aim of the study. To conduct a review of current literature dedicated to the problem of impaired neurodevelopment in children with hereditary diseases, to describe a clinical case of A. Rett genetic syndrome, accompanied by impaired neurodevelopment in a child. Materials and methods. The method of systematic and comparative analysis, as well as the biblio-semantic method of studying modern views on the influence of hereditary diseases in the disruption of neurodevelopment in children were used. As much as 25 recent publications were analyzed. A clinical case of A. Rett syndrome in a child is described, where the analysis of clinical symptoms and laboratory-instrumental examinations were used, the main of which is the molecular genetic method of next generation sequencing (NGS). Results. Based on the literature analysis it was estimated that clinical cases of rare A. Rett syndrome in children occur with a frequency of 1:10.000-1:15.000. This syndrome is caused by a mutation in the MECP2 gene associated with X-linked A. Rett syndrome/atypical A. Rett syndrome (UID MedGen: 48441) or X-linked MECP2 duplication syndrome (MedGen: 337496). Conclusions. For a long time, the connection of impaired neurodevelopment with other clinical symptoms was not payed much attention, but the enhanced frequency of cases when a child with impaired neurodevelopment was diagnosed with other symptoms or a multisystem lesion stimulated research in this area. This is the story how the term ″syndromal autism″ was born. This term means developmental delay or autism spectrum disorder in children with symptoms of another hereditary disease.

Неонатальний скринінг в Україні: розвиток, ефективність, перспективи

The aim of the work was to evaluate the results of screening for hereditary pathology among newborns in Ukraine. Research materials and methods: data from the official statistics of the Ministry of Health of Ukraine served as materials, a systematic approach and analytical methods were used: epidemiological, probabilistic and statistical. Data from official statistics on newborn screening for VVR for the period 2010-2022 were included in the analysis. Genetic screening is an effective tool for detecting congenital metabolic disorders. Reducing the frequency of births of children with congenital and hereditary pathology is possible under the conditions of state programs aimed at reducing the impact of risk factors that cause congenital anomalies, as well as measures to prevent their occurrence. In Ukraine, mass screening of newborns began to be carried out in 1992 only at FKU. Examinations for VH were selective (indicated by the presence of a relevant anamnesis) and became mass since 2006. From 2022, examinations for 21 rare diseases will be conducted. Conclusions: During the period 2010-2022, 67.4% of newborns were tested for cystic fibrosis, 86.3% for congenital hypothyroidism, and 90.7% for phenylketonuria. Full screening coverage is predicted to identify about 335 more children with the specified diagnoses. An important condition for increasing the efficiency of state programs of neonatal screening is the widespread informing of primary care doctors and future parents about the possibilities of prevention of orphan diseases.

Клинические случаи ранней офтальмологической диагностики септо-оптической дисплазии

Identification of a genetic variant of a hereditary disease of the visual organ is necessary not only to determine the features of clinical manifestations and course of the disease, but also to carry out preventive measures to prevent the birth of a sick child. Therefore, the identification of ophthalmopathology requires a mandatory assessment of the condition of the patient's body as a whole. The article presents two clinical cases of ophthalmological diagnosis of septo-optic dysplasia. It is a clinically heterogeneous condition representing a combination of hypoplasia of the optic nerves, pituitary hypoplasia and abnormal formation of structures along the midline of the brain. The diagnosis is established in the presence of two or more signs of the classical triad. Hypoplasia of the optic nerves leads to decreased vision, amblyopia. Violation of the hypothalamic-pituitary system requires hormone replacement therapy. The prognosis of mental development depends on central nervous system abnormalities, if any, mental retardation occurs. The first clinical case: a boy R., 11 months old, was directed by a neurologist due to the presence of a pendulum-like nystagmus, hypoplasia of the optic nerves of both eyes, uneven caliber and convoluted course of retinal vessels were also revealed upon examination. The lag in physical and neuropsychic development drew attention to itself. To clarify the diagnosis, the child was recommended to perform an MRI of the head, which revealed aplasia of the septum pellucidum. Septo-optic dysplasia was diagnosed on the basis of the revealed disorders. The second patient, a girl, 2 days old, was referred to an ophthalmologist by a neurologist, the absence of a septum pellucidum was revealed on the neurosonogram, hypoplasia of the optic nerves and tortuosity of the retinal vessels were found on examination of the fundus. Septo-optic dysplasia was diagnosed. Thanks to the early detection of this severe hereditary pathology, timely maintenance and replacement therapy by a neurologist and endocrinologist, and observation by a geneticist, it is possible not only to prevent complications of the disease itself, but also to prevent the re-birth of a sick child in the family. Keyword: septo-optic dysplasia; hypoplasia of the optic nerves; aplasia of the septum pellucidum

НАСЛЕДСТВЕННЫЕ ЗАБОЛЕВАНИЯ, ПРОТЕКАЮЩИЕ С ПОРАЖЕНИЕМ ПЕЧЕНИ (ЛЕКЦИЯ)

Background. Hereditary liver diseases are a serious problem in all age groups. Diagnosis of the hereditary liver disor-ders in many cases turns out to be difficult, and before final diagnosis, the patient can change more than one doctor and lose time, which can lead to a worsening of the disease. Therefore, the issue of timely diagnosis of hereditary liver diseases remains relevant. The lecture discusses the issues of diagnosing hereditary diseases occurring with liver damage. Both monogenic syndromes and multifactorial diseases are reviewed. Urea cycle disorders, aminoacidopathias and organic acidurias, lysosomal storage diseases, mitochondrial and peroxisomal diseases, disorders of fatty acids β-oxidation, carbohy-drate, lipid and cholesterol metabolism disorders and other diseases are described. The article describes the syndromes of liver disorders that occur in hereditary diseases; presents the combinations of individual syndromes having diagnostic significance. The pathogenetic aspects of the development of hepatic manifestations of hereditary diseases are considered. Conclusion. Symptoms of liver damage are often in the practice of any physician. Most of them are the manifesta-tions of somatic pathology. However, certain combinations of symptoms of liver damage (syndromes) indicate heredi-tary pathology. Therefore, it is extremely important to know the main liver syndromes in specific hereditary diseases, to understand the etiopathogenesis of such disorders and to carry out proper differential diagnosis.

Autoimmune polyendocrine syndrome type 1 in an 11-year- old boy

Autoimmune polyendocrine syndrome type 1 is a rare autosomal recessive hereditary pathology — a defect in the autoimmune regulator gene (AIRE), which develops with endocrine and non-endocrine manifestations in childhood. The disease is characterized by clinical polymorphism, which makes timely diagnosis difficult. The article describes a clinical case of an 11-year-old patient with autoimmune polyendocrine syndrome type 1, in whom the course of the disease was erased for a long period. The high quality of life of such patients is possible with timely, individually selected substitution therapy, followed by dispensary observation.

Search for germinal mutations in insulin-producing pancreatic tumors

BACKGROUND: It is known that insulinoma in approximately 5% of cases is associated with multiple endocrine neoplasia type 1 syndrome (MEN1), in which the prognosis and management tactics of patients have been developed in detail. The diagnosis of MEN1 often does not require genetic confirmation, since the syndrome has a typical clinical picture. At the same time, a combination of this tumor with other hereditary syndromes is found in the literature, which are characterized by the presence of malignant neoplasms of various localizations, primary multiple lesions, hormonal and other disorders. Thus, it is relevant to search for the genetic causes that cause the development of insulinoma, in addition to MEN1.AIM: to evaluate the frequency of detection of genetic causes of the development of insulin-producing tumors of the pancreas, in addition to MEN1; to analyze the phenotypic characteristics of patients with such tumors.MATERIALS AND METHODS: Based on the analysis of literature for the period up to 2020, a panel has been developed that includes coding regions of 10 genes (MEN1, VHL, TSC1, TSC2, KRAS, YY1, CDKN2A, MLH1, ADCY1, CACNA2D2) involved in the development of insulinoma. In 32 patients diagnosed with insulinoma, verified by pathomorphological examination, with the absence of clinical and/or genetic data indicating MEN1 syndrome, a panel of genes was sequenced with subsequent analysis of the identified genetic variants and phenotypic data obtained from the medical records of patients. In one patient, an additional molecular genetic study of the «Endom» panel was performed, revealing genetic variants of coding regions of 377 genes associated with endocrine diseases.RESULTS: In 8 patients (25%, 95% CI (11%; 43%)), 9 variants of mutations were identified that were not classified as benign, at that two mutations in the TSC2 gene were detected in one patient. Frequencies of genetic variants: TSC2 — 13%, 95% CI (4%; 29%), MEN1 — 6% (1%; 21%), MLH1 — 3% (0%;16%), CDKN2A/P16INK4A — 3% (0%;16%). When comparing patients with the identified mutation, with the exception of benign (n=8), and patients without mutation or with a benign mutation (n=24), there were no differences in the Grade (degree of differentiation), Ki67 proliferation index, frequency of concomitant tumors, burdened history, multiple pancreatic lesions or recurrence of insulinoma, however, patients with germinal mutation were found at the level of statistical trend to be younger at the manifestation of insulinoma and to have bigger tumors. In a patient who underwent an additional molecular genetic study using the new «Endome» panel, previously undescribed gene variants (APC and KIF1B) associated with various sporadic tumors, including endocrine ones, were identified.CONCLUSION: A panel of 10 genes has been developed, mutations of which are associated with insulinoma. A relatively high incidence of genetically determined insulinoma was determined (25% of cases), in half of cases — against the background of tuberous sclerosis. We consider it relevant to evaluate the effectiveness of genetic testing for patients with insulinoma. We believe that, first of all, patients with a high risk of hereditary pathology should be examined: with the manifestation of the disease at a young age and with a large tumor. The identification of a genetic mutation will make it possible to determine the prognosis of the disease, optimize the monitoring algorithm in order to timely identify concomitant diseases-components of the hereditary syndrome, and conduct genetic counseling of the family.

SYNDROMAL APPROACH IN THE DIAGNOSIS OF HEREDITARY DISEASES (LECTURE)

The number of nosologic units of hereditary pathology is, according to Online Mendelian Inheritance in Man, about 16,000 syndromes (and their corresponding genes). Before starting diagnostics, it is necessary to make sure that the disease is genetically determined, using such signs as the familial and congenital nature of the pathology, progressive chronic course, multiplicity of pathological changes in organs and systems, resistance to known meth-ods of therapy. For effective diagnosis, it is necessary to use the assessment of minor and major developmental anomalies, as well as a syndromic approach. The syndromic approach is used to diagnose functional and anatomical syndromes that accompany hereditary diseases. This allows you to narrow the range of diseases to the use of labora-tory and instrumental research methods, and most accurately formulate a preliminary diagnosis for DNA diagnostics. Diagnosis of hereditary pathology is a rather complex problem because the number of nosologic forms is large, and the final diagnosis is determined using expensive DNA diagnostics. In this regard, the possibility of using a syn-dromic approach in clinical diagnosis comes to the fore

КЛИНИЧЕСКИЙ СЛУЧАЙ СИНДРОМА ЧЕРЕПНО-КЛЮЧИЧНОГО ДИЗОСТОЗА: КЛИНИЧЕСКИЕ И РЕНГЕНОЛОГИЧЕСКИЕ ПРОЯВЛЕНИЯ

Objectives. Clinical case in the practice of an oral and maxillofacial surgeon: a child with cranioclavicular dysostosis. This cider was first described in 1898 by P. Marie and P. Sainton. H. Scheuthauer described the pathological manifestations of skeletal anomalies in more detail. Steithauer–Marie–Sainton syndrome, or cranioclavicular dysostosis, involves aplasia or hypoplasia of the clavicles, delayed dentition, supernumerary teeth, and other skeletal abnormalities. In this syndrome, skeletal abnormalities include clavicular aplasia, or hypoplasia, bell-shaped chest, enlarged cranial vault with a convex frontal bone, open fontanelle, brachydactyly, pelvic hypoplasia, short stature, severe abnormal development of teeth with changes in occlusion, that is, this is a fairly severe hereditary pathology . Retention and dystopia of permanent teeth are associated with the presence of one or more supernumerary teeth on the upper and lower jaws.
 Purpose. Conducting an anthropometric, dental, and x-ray examination of a child with cranioclavicular dysostosis.
 Methodology. The article presents photographs of the child, pediatric and dental examination data, plain radiography of the chest and collarbones, orthopantomography of the upper and lower jaw, and a treatment plan for cranioclavicular dysostosis. Currently, due to a problem with teething, she consulted a dentist; after an examination, the child was referred to a maxillofacial surgeon.
 Conclusions. Cranioclavical dysostosis syndrome is a complex congenital pathology, the complex rehabilitation of which should involve not only doctors of all dental specialties, but also maxillofacial surgeons, orthopedists, pediatricians, neurologists, speech therapists, and medical psychologists.

ORGANIZATION OF PREVENTION, EARLY DETECTION AND TREATMENT OF GENETICALLY DETERMINED OPHTHALMOLOGICAL PROBLEMS IN AZERBAIJAN

The aim of this research is to present an optimized plan for organizing the prevention, early detection and treatment of genetically determined eye problems. Materials and methods. The study focuses on the process of prevention, detection and treatment of hereditary eye pathology. Specifically, it addresses issues related to the timely detection of genetically determined ophthalmic diseases leading to patient disability. The study included patients of the Acad. Zarifa Aliyeva National Centre for Ophthalmology, Baku. The study employs patient survey, analytical mapping, and statistical processing of the findings obtained. Results. Genetically determined pathology of the eye occurs quite often, this problem is most common in those countries where the percentage of consanguineous marriages is high. In some cases, hereditary pathology causes disability from early childhood. The correct approach to the problem of detecting the presence of abnormalities in early pregnancy, timely diagnosis and treatment in many cases helps to avoid the birth of children with genetic abnormalities and preserve the vision of sick patients. The organization of assistance to this category of population is multi-staged and involves various organizations not related to health care. An important role is played by the level of financial capabilities and the state of medical institutions, as well as the qualifications of the staff. The first stage of assistance to the population is to identify a risk group. At stage 2, a genetic study of the foetus is carried out in mothers included in the risk group. During stage 3, dynamic control is exercised over a newborn child from a risk group. Stage 4 is the organization of medical and surgical care for patients. The creation of a clear system of informing and helping patients with genetic abnormalities will reduce the number of visually impaired people. Conclusion. Thus, it is necessary to create a clear system of medical and preventive care for children with genetic abnormalities. Only the joint work of social services and doctors of different specialties can lead to successful results in providing care to this group of patients.

Multisystem inflammatory syndrome complicated by pulmonary embolism in a child

Purpose - to present a clinical case of a particular complication of post-COVID multisystem inflammatory syndrome (MIS) - pulmonary embolism (PE) which developed due to primary hereditary thrombophilia in a child for better understanding of the MIS evolution and prognosis in children (MIS-C). Case report. In an 11-year-old boy who previously had no hemorrhagic manifestations, the first symptoms of the disease occurred in the form of fever and a hemorrhagic rash on the lower extremities. Later, he developed signs of respiratory failure, his condition worsened, and bilateral community-acquired viral pneumonia caused by COVID-19 was diagnosed. The child presented with post-COVID MIS manifested as PE, which caused further genetic examinations for hereditary thrombophilia. Primary thrombophilia was detected (F2 gene - prothrombin (20210 G>A) D68.5). Concomitant hereditary pathology was probably the reason for a severe course of the infection and the development of a complication in the form of PE requiring intensive and long-term anticoagulant therapy. Conclusions. In case of PE detection, especially in young patients, examinations to confirm or rule out hereditary or acquired thrombophilia are required, that defines recurrent venous thromboembolism prevention programs. This clinical case report is a contribution to the study on the issues of MIS-C, defining links between pulmonary complications (transient or persistent) and serious sequelae in the future. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Topical issues in pediatric ophthalmogenetics: diversity and prevalence of hereditary eye pathology

According to the World Health Organization, hereditary eye pathologies (HEP) constitute a significant proportion of ophthalmologic diseases (at least 35% in total and up to 40%in children), resulting in substantial disability (65-70%). However, there is a lack of data on the prevalence and diversity of HEP in the Russian Federation. Therefore, it is crucial to study the prevalence and etiological nature of these diseases using modern genome technologies, in order to identify frequent forms, enable early detection in children, and develop effective therapeutic and preventive measures. Objective: The objective of this study was to estimate the prevalence of HEP in children, both as isolated conditions and as part of hereditary diseases and syndromes, in seven regions of the Russian Federation, while identifying frequently occurring nosological forms. Materials and methods: An epidemiological and clinical genetic study was conducted in 60 districts across the regions of Rostov, Kirov, Republics of Chuvashia, Udmurtia, Bashkortostan, Tatarstan, and Karachay-Cherkessia, encompassing a total population of 2,434,460 individuals, including 480,575 children. The study encompassed the entire population of the selected areas, regardless of age, and followed an original protocol for genetic and epidemiological research established at the Laboratory of Genetic Epidemiology. The methods employed included clinical-genetic, genealogical, clinical-laboratory, and molecular-genetic techniques, such as full-exome sequencing. The prevalence of visual organ diseases was calculated. Results: The results revealed a total of 449 patients with 56 different forms of isolated hereditary eye pathology (IHEP), indicating a prevalence of 1:1070 children. Additionally, 507 pediatric patients were identified with eye involvement as a symptom of 50 hereditary diseases and syndromes (SHEP), resulting in a prevalence of 1:954 children. Overall, hereditary eye lesions affecting various eye structures were identified in 956 pediatric patients, yielding a prevalence of 1:504 children. Frequent nosological forms were identified for both disease groups: 17 in IHEP and 14 in SHEP. Notably, these frequent hereditary eye diseases accounted for more than 80% of all identified patients with hereditary pathology (83.30% and 88.10% for IHEP and SHEP, respectively). Conclusion: This study provides new insights into the epidemiology of hereditary eye pathologies in the Russian Federation and describes frequent diseases within this population. These findings will contribute to improving research and clinical practices, expanding the range of treatable conditions, and informing targeted programs and measures in the field of children’s healthcare.

Morphological features of a patient with progeroid phenotype

Currently, in medical genetics, there is a significant gap between real medical care and scientific achievements in the field of molecular biological technologies. The diagnosis of hereditary pathology is made infrequently, and genetic knowledge is slowly entering medical practice. Most patients with hereditary disorders are under completely different diagnoses and are treated by specialists according to the principle of the leading clinical symptom, such as, for example, mental retardation, skeletal deformities, ocular pathology, hearing loss, atrophic, ichthyosis-like or psoriasiform skin changes, etc. The clinic of hereditary diseases is often similar to well-known and frequently occurring diseases, since there is a phenotypic similarity of genetically heterogeneous diseases. Misdiagnosis leads to pathogenetically unjustified treatment. In our work, we described a clinical case of progeroid syndrome that confirmed by cytogenetic diagnostics based on the Pavlov University (Saint Petersburg, Russia). The patient has been observed with various dermatological syndromes for 26 years. With a multidisciplinary approach to the verification of hereditary disease, dermatovenerologists and geneticists were able to define the hereditary nature of the skin lesion in the patient and confirm her progeroid syndrome.

Hemostasis System in Airline Passengers and Pilots

This review contains the results of the studies of the hemostasis system in airline passengers and crew members, as well as ground-based model experiments simulating the effect of specific flight factors. According to most researchers, flight factors shift the coagulation balance towards increasing the procoagulant potential. However, the occurrence of thrombotic conditions in passengers is associated with the individual presence of certain endogenous risk factors, such as age, constitution, the diseases of the cardiovascular system and hereditary pathology of the hemostasis system, some types of hormone therapy. Aircraft pilots whose flight time significantly exceeds that of passengers have described cases of thrombosis. No mention of cases of hemorrhagic conditions in civil aviation flight personnel has been found in the available literature.

Medullary thyroid cancer: epidemiology

Epidemiology of medullary thyroid cancer is presented in the literature review. Thyroid cancer is the most common form of endocrine oncological pathology. It accounts for 96–97 % of all malignant tumors of endocrine organs. According to the Surveillance, Epidemiology, and End Results Program (USA), the incidence of thyroid cancer in 1975–2009 increased approximately threefold, from 4.9 to 14.3 cases per 100,000 population. At the same time, the mortality rate remained low, approximately at the same level, 0.5 cases per 100,000. Such a situation can be explained to some extent by the improvement of diagnostic capabilities of the early, often preclinical, stage of thyroid tumors. Medullary thyroid cancer ranks third after papillary and follicular cancer, but surpasses them in terms of aggressiveness. It is a re­latively rare disease. This type of tumor makes up 1–9 % of all thyroid cancers. Against the background of the general tendency to increase the incidence of thyroid cancer, the absolute number of cases of medullary cancer according to various data remains relatively stable. Epidemiological characteristics of medullary thyroid cancer deserve attention in the age aspect, as well as when considering the frequency of detecting these tumors at autopsy of people who had no signs during their lifetime. In clinical practice, medullary thyroid cancer occurs in two main forms — sporadic and hereditary. The latter is represented as part of the combined syndrome of multiple endocrine neoplasia type 2 (MEN-2), which, in turn, is divided into two subtypes: MEN-2A and MEN-2B syndromes. MEN-2 syndrome is a rare combined hereditary pathology. Sporadic medullary thyroid cancer accounts for approximately 70–80 % of such tumors. It is accompanied by other types of endocrinopathies. Most cases of medullary thyroid cancer occur in the fifth decade of life. The presented data on the epidemiology of medullary thyroid cancer allow for a more detailed and in-depth study of this pathology and contain a certain amount of useful and necessary information.

Neurodevelopmental Manifestations and Birth Defects in Prader-Willi Syndrome: Findings from a Study in Western Ukraine

Prader-Willi syndrome (PWS) is a genetic disease characterized by mental retardation, as well as autism spectrum disorders, obesity and mood disorders. The aim of our study was to research a spectrum of genetic heterogenity and different clinical neurodevelopmental manifestations. Materials and methods: clinical, molecular, genetic and psychological methods were used. We observed 9 children (5 boys and 4 girls) with Prader-Willi syndrome from Lviv and Ivano-Frankivsk regions (Western Ukraine) who were diagnosed and followed-up at the Institute of Hereditary Pathology, National Academy of Medical Sciences of Ukraine, Lviv, for 4 years (2019–2022) and underwent molecular genetic testing. The ages of children ranged from 1 month to 7 years, with the mean value amounting to 3.6 years of age. Results: Our study revealed that 6 (66.7%) out of 9 children with PWS had birth defects. At ultrasound during pregnancy, we observed certain clinical features of the fetus, including fetal intrauterine development delay –5 (55.5%), and higher nuchal translucency measurement – 3 (33.3%). According to the checklist of autism spectrum disorders (CASD), 3 of the examined children with autism syndrome were at risk and required further monitoring, while 5 children scored 18-20 points, which indicated the presence of autistic spectrum and required in-depth monitoring during diagnosis. Stereotypical and repetitive play as a manifestation of problems with social interaction was observed in 3 boys with PWS. In our study, parents had no complaints about aggressive behavior in children with this syndrome. Conclusions: In cases if the children have signs of autism or developmental delay, they should undergo genetic counseling.

Aislamiento y caracterización de vesículas extracelulares enriquecidas en exosomas en pacientes españoles con enfermedad de Dent 1

Background and objectivesDent's disease type 1 (DD1) is a rare X-linked hereditary pathology caused by CLCN5 mutations that is characterized mainly by proximal tubule dysfunction, hypercalciuria, nephrolithiasis/nephrocalcinosis, progressive chronic kidney disease, and low-weight proteinuria, the molecular hallmark of the disease. Currently, there is no specific curative treatment, only symptomatic and does not prevent the progression of the disease. In this study we have isolated and characterized urinary extracellular vesicles (uEVs) enriched in exosomes that will allow us to identify biomarkers associated with DD1 progression and a better understanding of the pathophysiological bases of the disease. Materials and methodsThrough a national call from the Spanish Society of Nephrology (SEN) and the Spanish Society of Pediatric Nephrology (AENP), urine samples were obtained from patients and controls from different Spanish hospitals, which were processed to obtain the uEVs. The data of these patients were provided by the respective nephrologists and/or extracted from the RENALTUBE registry. The uEVs were isolated by ultracentrifugation, morphologically characterized and their protein and microRNA content extracted. ResultsTwenty-five patients and 10 controls were recruited, from which the urine was processed to isolate the uEVs. Our results showed that the relative concentration of uEVs/ml is lower in patients compared to controls (0.26×106 vs. 1.19×106uEVs/ml, P<0.01). In addition, the uEVs of the patients were found to be significantly larger than those of the control subjects (mean diameter: 187.8 vs. 143.6nm, P<0.01). Finally, our data demonstrated that RNA had been correctly extracted from both patient and control exosomes. ConclusionsIn this work we describe the isolation and characterization of uEVs from patients with DD1 and healthy controls, that shall be useful for the subsequent study of differentially expressed cargo molecules in this pathology.