Autosomal Dominant Type Of Inheritance Research Articles

#805 Successful application of DALI for extracorporeal hemocorrection in a patient with LDL cholesterol serum levels (case study)

Abstract Background and Aims Plasma lipoidosis type 4 (PLD4) is a rare hereditary disease characterized by disorders of fat metabolism in the body. PLD4 occurs rare in the general population. The exact frequency of occurrence is unknown, as it depends on hereditary factors in a particular population. The relevance of the disease lies in its rarity and potential association with various complications. Patients with PLD4 have decreased levels of low-density cholesterol (LDL) and increased levels of triglycerides in the blood, which can lead to the development of atherosclerosis and other cardiovascular diseases. Plasma lipoidosis type 4 requires further researches for better understanding of its epidemiology, mechanisms of development and possible treatment strategies. In this case, we describe the case of a patient with type 4 plasmatic lipoidosis who was treated with the DALI (Direct Adsorption of Lipoproteins) technique. Anticoagulation is initiated with heparin and maintained by ACT. This technique is accompanied by decreasing the level of LDL and Lp (a) without decreasing the level of HDL and fibrinogen. The pore sizes of the polyacrylamide bed are small enough to avoid the removal of red blood cells and platelets. Activation of leukocytes and complement is minimal and clinically insignificant. Depending on the initial level of lipidemia during this procedure, it is possible to select the appropriate adsorber (DALI-500, -750, -1000). Methods of extracorporeal correction of lipid metabolism disorders should be widely introduced into healthcare practice. It should be noted that during DALI apheresis, the fibrinogen level does not decrease so sharply and is not accompanied by changes in erythrocyte aggregation. (Richter W. O., 2003). Aim of study The purpose of our study was to evaluate the effectiveness of using DALI (Direct Adsorption of Lipoproteins) in a patient with type 4 plasmatic lipoidosis. Method Patient N., 67 years old, diagnosed with IHD. Angina pectoris FC 2. Plasma lipoidosis type 4, hyperbetalipoproteinemia by autosomal dominant type of inheritance. Cysts of both kidneys. In 1997, diagnosed with: plasma lipoidosis type 4, hyperbetalipoproteinemia by an autosomal dominant type of inheritance. The plasmapheresis sessions were recommended against the increased lipid metabolism indexes. The patient regularly receives antilipidemic therapy and plasmapheresis sessions up to 2 times a year. The patient is admitted with complaints of fatigue and general weakness. According to the patient's ambulatory card, discharge summaries: CREA - 147 µmol/l, UREA – 6.3 mmol/l. GFR – 34 ml/min/1.73 m2. Total bilirubin - 9 µmol/l, direct bilirubin - 3 µmol/l. Considering the severity of the condition and the activity of the main diagnosis, a procedure with the DALI technique was started. During the hospitalization period, 3 procedures were performed, the whole of them were tolerated satisfactorily. The general condition is of moderate severity. Consciousness is clear. Hemodynamics is stable. Urination is free and painless. Diuresis is adequate. Results Hemodynamics: when connected - blood pressure – 120/82 mm Hg, heart rate – 61 beats/min. When disconnected, the patient's condition is the same, hemodynamics - blood pressure – 119/59 mm Hg, heart rate – 65 beats / min. Conclusion The usage of the apheresis method with the DALI system can effectively reduce the level of low-density lipoprotein (LDL) and Lp (a), while maintaining the content of high-density lipoprotein (HDL) and fibrinogen at a constant level. This reduction in LDL concentrations has the potential to reduce patients' risk of developing cardiovascular disease and the mortality from it.

Effectiveness and safety of PCSK9 inhibitors in children with family hypercholesterolemia

Familial hypercholesterolemia (CGHS) is a monogenic disease with a predominantly autosomal dominant type of inheritance, accompanied by a significant increase in the level of low-density lipoprotein cholesterol in the blood, and as a result, premature development and progressive course of atherosclerosis, usually at a young age. One of the common causes of the disease is a mutation in the PCSK9 gene. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the main link in the regulation of blood lipid metabolism due to its direct participation in the degradation of LDL receptors. Currently, only evolocumab is used as PCSK9 inhibitors in children over 12 years of age in the Russian Federation, which has proven the safety and steady reduction of LDL cholesterol in pediatric patients with HES. Another representative of this pharmacological group is alirocumab, which is currently indicated only for people over the age of 18, due to the lack of evidence in children.

Combination of Psoriasis and Vitiligo in a Child with Sotos Syndrome: Clinical Case

Background. Psoriasis and vitiligo are chronic, relatively common dermatological diseases. Meanwhile, their combination in children is rare. The combination of psoriasis and vitiligo in a child with Sotos syndrome has not been previously described. Clinical case description. The boy, 10 years old, was hospitalized with complaints (according to his mother) of rashes on the scalp, body, and limbs, with mild itching that was not related to the time of day. The pathological skin process was widespread. The patient was hyperactive, restless, emotionally labile, irritable. Complaints of rashes was mentioned firstly at the age of 7. Sotos syndrome was established at the age of 8 (variant c.6559C>T (p.Arg2187Ter) in 23 exon of the NSD1 gene (5q35.3), autosomal dominant type of inheritance (pathological allele de novo)). Psoriasis vulgaris was diagnosed with secondary vitiligo (localized form) at the age of 8.5 years. Symptomatic antipruritic and external pathogenetic therapy was performed in the hospital. Phototherapy was not prescribed due to the relative contradiction (small retrocerebral cyst) and the peculiarities of major disease (hyperactivity, restlessness) that complicated to place the child in the phototherapy booth. Positive dynamics was noted during the treatment (14 days): no itching, decrease of peeling severity, flattening and blanching of psoriatic rash elements to spots of post-inflammatory hypopigmentation. The lesion (focus of depigmentation) on the right knee joint skin remained unchanged. The patient was discharged to outpatient care. The prognosis for Sotos syndrome and skin lesions is favorable. Conclusion. The first medical observation of the child with Sotos syndrome burdened with psoriasis and vitiligo is presented. The pathogenetic correlation of these diseases is not clearly defined. Management of such cases requires the joint collaboration of dermatologists, geneticists and pediatricians.

Surgical treatment of hereditary pancreatitis in four children in one and the same family

BACKGROUND: Hereditary pancreatitis is an autosomal dominant disease with high gene penetration (80%), manifested with signs of chronic and recurrent pancreatitis. This pathology is rarely met in children. In the world literature, the idea of surgical approach in treating hereditary pancreatitis is evidently supported because it helps to eliminate symptoms of pancreatic obstruction, to prevent complications and to slow down the process of pancreatic atrophy. CLINICAL CASE DESCRIPTION: The article describes a case of hereditary pancreatitis with an autosomal dominant type of inheritance, with a mutation in PRSS1 gene in children in one and the same family. Due to the longitudinal pancreatic jejunostomy, patients could have a good clinical remission. CONCLUSION: The discussed clinical case describes a successful surgical technique which has given good outcomes in treating hereditary pancreatitis in children.

Peitz–Jaegers syndrome as a cause of intussusception in children

BACKGROUND: Intestinal intussusception is a common cause of acute intestinal pathology in children. Peitz–Jaegers syndrome is a rare disease with an autosomal dominant type of inheritance characterized by the development of hamartomic polyps in the gastrointestinal tract and pigmented spots on the skin and mucous membranes. It is a “precancerous” state which increases the risk of oncologic formations in the gastrointestinal tract and in genital glands. Peitz–Jaegers syndrome is associated with mutations in STK11 or LKB1 genes.
 CLINICAL CASE DESCRIPTION: The article describes the authors’ experience in surgical resolution of the intestinal intussusception with atypical course in a 6-year-old child. Diagnostic laparoscopy detected intussusceptions in the small intestine, one of which was immediately desinvaginated with instruments and the other one required conversion. During the surgery, dense tumor-like formations were identified; therefore, jejunum loop with revealed formations was resected. Further histological and other testings showed that these formations were hamartomic polyps. The patient had been preliminary diagnosed with Peitz–Jaegers syndrome which further was confirmed by genetic and histological analyses and gastroscopic examination. The postoperative period was uneventful; the child was discharged in the satisfactory condition on day 7 after the surgery.
 CONCLUSION: Consultations with a pediatric surgeon and gastroenterologist, examination of the upper and lower gastrointestinal tract, monitoring polyps’ onset or growth are stages of key importance in children with Peitz–Jaegers syndrome. Such an approach promotes minimization of risks associated with the course of this disease. To prevent emergency surgical situations, it is important to make genetic analyses for children with the family history of polypous syndrome in the gastrointestinal tract.

CLINICAL CASE OF FAMILIAL TUBEROUS SCLEROSIS

Relevance. Tuberous sclerosis is a genetic disease with an autosomal dominant type of inheritance, characterized by the presence of benign tumors in various organs, a progressive course leading to disability and a decrease in life expectancy.
 Clinical case. The pregnant's MRI of the brain revealed the presence of tubercles in the area of the cerebral cortex. At the time of 34 weeks of pregnancy, the presence of endocardial nodular formations in the fetus was revealed prenatally. MRI of the fetal brain showed the presence of a subependimal node in the area of the basal nuclei on the left. Postnatally: MRI-picture of multiple cortical-subcortical tubers, subependimal nodes, ECHO-CG-picture of multiple formations in the cavities of the heart. DNA diagnostics: the extended deletion of the TSC2 gene was determined.
 Discussion. During ultrasound of the 3rd screening of the fetus, large endocardium formations were found, which made it possible to suspect tuberous sclerosis. During the examination of the newborn, the diagnostic assumptions identified prenatally were confirmed. Since tuberous sclerosis has an autosomal dominant type of inheritance, it can be assumed that the pregnant has a high probability of having the same diagnosis.
 Conclusion. An integrated approach to the diagnosis of this disease allows you to pay attention to the patient in a timely manner and choose the appropriate treatment tactics.

Differential diagnosis of juvenile idiopathic arthritis and multiple epiphyseal dysplasia: Experience of multidisciplinary interaction

Introduction. Juvenile idiopathic arthritis (JIA) is a common multifactorial disease characterized by the presence of chronic inflammation in the joints, entheses and other structures of the musculoskeletal system in combination with a certain range of extraskeletal disorders. Vast variety of JIA clinical variants and the variability of the disease course make primary and differential diagnosis difficult, which often leads to a delayed start of treatment and an inadequate choice of medical therapy or, conversely, an excess of medication. In the range of differential diagnostic conditions that have similar symptoms and are manifested by severe arthralgia, gait disturbance, joint stiffness, as well as the presence of effusion and gradual progression of bone destruction mainly in the epiphyseal plate, one should remember about hereditary skeletal dysplasias, primarily from a genetically heterogeneous group of multiple epiphyseal dysplasias (MED). The aim of the study – description of the clinical and genetic characteristics of three patients with various genetic variants of MED and defining approaches for their differential diagnosis with JIA. Materials and methods. There were three patients from three unrelated families aged from 7 to 13 years old under our supervision. To clarify the diagnosis, a genealogical analysis, a clinical examination of patients and first-degree relatives, as well as an assessment of X-ray images of long tubular bones were carried out. Molecular genetic confirmation of the MED diagnosis types 1 and 2 was based on the results of custom panel sequencing consisting of 166 genes responsible for the development of hereditary skeletal pathology. To clarify the molecular genetic diagnosis of MED type 4, an analysis of the SLC26A2 gene was performed using automated Sanger sequencing. Results. Anamnestic, clinical, radiological, and molecular genetic characteristics of three unrelated patients with different genetic types of MED caused by variants in the COMP, SLC26A2, and COL9A2 genes were analyzed. The first symptoms of the disease in observed patients with three different genetic variants of MED occurred at the age of 2–3 years old and were characterized by gait disturbance and climbing stairs difficulties. Gradually, these symptoms were accompanied by pain in large joints. According to the ultrasound examination of the joints, signs of synovitis were noted, as a result they were diagnosed with JIA (polyarticular variant, seronegative for rheumatoid and antinuclear factor) and immunosuppressive therapy were prescribed without significant effect. The atypical course of the JIA was the reason for additional examination of patients by an orthopedist and geneticist. Careful analysis of the large joints radiographs made it possible to suspect one of the variants of MED in our patients based on the detection of distinctive signs, which were characterized by abnormal ossification (diminished size and flattening) of the epiphyses and abnormal shape and structure of the femoral head epiphysis. Molecular genetic analysis was performed to confirm the diagnosis. As a result, a pathogenic variant of the nucleotide sequence in the COMP gene was detected in one of the patients, two pathogenic variants in the SLC26A2 gene in another patient, and one pathogenic variant in the COL9A2 gene in the third patient, which made it possible to confirm the final diagnosis of MED type 1 with an autosomal dominant type of inheritance, MED type 4 with an autosomal recessive type of inheritance and MED type 2 with an autosomal dominant type of inheritance, respectively. Based on the results of our own research and analysis of the literature data, key directions for the differential diagnosis of MED and JIA were formulated. It is shown that the analysis of the X-ray images of patients is essential in differential diagnosis. Conclusion. Despite the significant overlap of the clinical symptoms between JIA and MED, the key to the early diagnosis of MED is a comprehensive examination, which included genealogical analysis, features of clinical manifestations and disease course in combination with distinctive radiological signs including delayed ossification of the epiphyses of tubular bones typical for MED. However, the question remains about the probability of a combined nature of osteoarticular disorders, i. e., the possible development of JIA in patients with hereditary skeletal dysplasias which requires in-depth study in the future.

Clinical and genetic aspects of glaucoma associated with congenital aniridia

Congenital aniridia is a hereditary congenital malformation of the visual organ with an autosomal dominant type of inheritance. The prognosis for vision largely depends on the development and progression of multiple complications (glaucoma, keratopathy, and aniridia fibrotic syndrome) at different ages.
 AIM: To identify the most significant risk factors for glaucoma development and a poor prognosis associated with congenital aniridia.
 MATERIAL AND METHODS: Seventy-three children (146 eyes) with PAX6-associated aniridia aged 016 yr were examined, with 41 males (56.2%) and 32 females (43.8%). The follow-up period of patients ranged from 2 to 6 yr. Thirty-five (47.9%) patients had complete aniridia, and 38 (52.1%) patients had partial aniridia. All patients underwent a comprehensive ophthalmological and molecular genetic examination.
 RESULTS: Glaucoma developed in 28.8% of children. Anomalies in the anterior chamber angle (ACA) structure were detected in most patients with congenital aniridia, both with and without glaucoma. However, the relationship between the ACA and the timing of the manifestation of glaucoma was revealed. Furthermore, according to our study, the presence of glaucoma increases the risk of keratopathy progression.
 CONCLUSION: In a molecular genetic study, the presence of deletions in the 3'-cis-regulatory region of the PAX6 gene was a predictor of glaucoma development.

Clinical characteristics of different forms of myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is one of the most common neuromuscular diseases with an autosomal dominant type of inheritance associated with expansion in the DMPK gene. A distinctive feature of the disease is the presence of muscle symptoms and multisystemic. Depending on the age of onset and the number of CTG repeats, there are congenital, infantile, juvenile, classic (adult) form and a form with a late onset. Each form is characterized by its own features of the onset, course of the disease, heterogeneity of clinical manifestations, which makes it difficult to make a timely diagnosis. Increasing the awareness of physicians of all specialties about the nature of the course of various forms will make it possible to diagnose MD1 at an earlier stage, improve the prognosis and quality of life of patients. The article provides a literature review that demonstrates the spectrum of clinical manifestations in various forms of MD1.

Hereditary keratoderma of Unna-Tost in a patient with atopic dermatitis

Unna-Toast's keratoderma is a disease belonging to the group of genodermatoses with an autosomal dominant type of inheritance and characterized by hyperkeratosis on the palms and soles. This nosology can manifest itself at any age as an independent process, but more often it debuts at 12 years of age, in some cases combined with various congenital malformations of ectodermal origin.
 The prevalence of this disease ranks second among hereditary dyskeratoses, however, it is rare in the practice of a dermatologist and there are no static data on the disease.
 The article presents a clinical observation of Unna-Toast's keratoderma that first appeared against the background of atopic dermatitis. The clinical picture is represented by smooth yellow horny layers located on the palms and soles, with a sharply defined border and an erythematous corolla along the periphery. Other areas of the skin are represented by lichenification foci with small-lamellar peeling, excoriations and serous-hemorrhagic crusts on the surface.
 This clinical case confirms the possibility of manifestation of hereditary hyperkeratosis against the background of aggressive atopic dermatitis. Unna-Tost's keratoderma is of high interest in the practice of a dermatologist and requires a detailed description of the available clinical cases, due to the rare occurrence of this nosology in the population.

Clinical features of hypertrophic cardiomyopathy depending on the hereditary factor

The objective was to study the clinical features of symptomatic hypertrophic cardiomyopathy (HCM) depending on the form (familial / non-familial), the age of onset and the presence of arterial hypertension (AH).Methods and materials. During 6 years, we examined 250 HCM patients, 100 patients with symptomatic HCM aged from 18 to 86 years were included in the study. Results. Patients with the clinical manifestations onset at a young age more often had a familial form of the disease, an autosomal dominant type of inheritance, an asymmetric HCM with reverse curve interventricular septal morphology. On the contrary, patients with the clinical manifestations onset at the age of ≥45 years had non-familial form of the disease and asymmetric HCM with basal interventricular septal hypertrophy. The young HCM patients with associated AH more often were obese, had CHF of III–IV functional class (NYHA), larger anteroposterior left atrial diameter than patients without AH and more often needed interventricular septal reduction. HCM patients and associated AH with the disease onset at the age of ≥45 years significantly more often had angina syndrome. Absolute indications for interventricular septal reduction in HCM patients with the disease onset ≥45 years of age were determined only for HCM patients and associated AH. At the same time, 50 % of HCM+AH patients both at a young age and in the older group, had obesity. Conclusions. The interventricular septal morphology differs significantly depending on the age of clinical manifestations onset. Co-existing AH and obesity are predictors of the progressive HCM course and an increase in the proportion of patients with absolute indications for interventricular septal reductions regardless of the age of clinical manifestations onset.

Эктопические ресницы как фактор риска возникновения язв роговицы у собак. Особенности клинической картины, диагностики и лечения

This paper presents a generalized experience of diagnosis and treatment of dogs with ectopic eyelashes and corneal ulcers caused by them. Ectopic eyelashes are ophthalmopathy, which is most common in dogs and is characterized by the germination of pathological eyelashes or eyelashes through the tarsal plate and conjunctiva of the upper eyelid from hair follicles, and have a damaging traumatic effect on the cornea, causing erosion and then corneal ulcer. The pathology is congenital and has an autosomal dominant type of inheritance. There is also a pedigree predisposition to this disease. The following breeds are most susceptible: Brussels Griffin, Brabanson, Retriever, Pekingese, Shih Tzu, Cavalier King Charles Spaniel, boxer, English Bulldog, English Cocker Spaniel, Poodle, Jack Russell Terrier and Yorkshire Terrier. The main problem of the appearance of ectopic eyelashes is the occurrence of erosions and corneal ulcers in the projection of eyelash growth. Which is accompanied by a pronounced pain syndrome, which manifests itself in the form of photophobia, blepharospasm, lacrimation and / or suppuration, corneal edema and the desire of the animal to constantly scratch the eye. In this work, a study was conducted to determine the risk factors for the occurrence of this pathology (this is a breed predisposition and genetic inheritance), diagnosis and effectiveness of surgical treatment of this pathology on 50 dogs. The authors describe the clinical picture, the technique of the operation, and the results of dynamic observation of animals. According to the results of clinical observations, it was found that there is a characteristic breed predisposition and genetic inheritance of ophthalmopathy. This factor must be taken into account during the clinical examination of the animal. Also, when ectopic eyelashes appear, a fairly characteristic clinical picture of the disease is observed. The surgical method of V-plastic surgery is proposed for treatment. No relapses were recorded in any of the 50 cases examined, while the morphofunctional characteristics of the cornea were preserved. Drug maintenance therapy, including a regenerative drug, showed good results in the postoperative period. The use of a regenerative drug accelerated the healing process, allowed to preserve the transparency of the cornea and its curvature.

СИНДРОМ БРУГАДА В КЛИНИЧЕСКОЙ ПРАКТИКЕ

Brugada syndrome is a congenital channelopathy with an autosomal dominant type of inheritance and low penetrance, characterized by the presence of a typical clinical and electrocardiographic symptom complex, including a special form of blockade of the right bundle branch block with ST segment elevation in one or more right chest leads on the electrocardiogram, the absence of organic pathology of the heart and various life-threatening ventricular arrhythmias, which can lead to the development of sudden cardiac death. The article defines the concept of "Brugada's syndrome", the geography and frequency of occurrence of the disease. It is indicated that more than 450 pathogenic variants in 24 genes are involved in the development of Brugada syndrome. The article presents two main hypotheses of pathogenesis, describes the electrocardiographic picture, three types of ECG changes, clinical manifestations and classification of the Brugada syndrome. Listed diseases with which it is necessary to carry out differential diagnosis of Brugada syndrome. Various aspects of the treatment of Brugada syndrome are presented: non-drug methods, pharmacotherapy, installation of an implantable automatic cardioverter-defibrillator, epicardial catheter ablation of abnormal areas of the anterior part of the outflow tract of the right ventricle.

Клинический случай поздней диагностики наследственного микросфероцитоза

Hereditary spherocytosis is a congenital hemolytic anemia, with an autosomal dominant type of inheritance, characterized by a violation of the structure of the erythrocyte membrane (microspherocytosis), increased osmotic fragility of erythrocytes, excessive destruction in the vasculature of the spleen, with a pronounced favorable response to splenectomy. Excessive destruction of red blood cells leads to anemia, reticulocytosis, hyperbilirubinemia (due to the indirect fraction) followed by cholelithiasis. The factor that aggravates the course of microspherocytosis is folate deficiency, which can appear both in people with limited nutrition and in pregnant women.

МЕДУЛЛЯРНАЯ ГУБЧАТАЯ ПОЧКА: КЛИНИЧЕСКИЕ И РЕНТГЕНОЛОГИЧЕСКИЕ ПРОЯВЛЕНИЯ

The paper describes a case of medullary sponge kidney with gross hematuria in a 69-year old woman. The case is of interest due to the rarity of the disease and the difficulty of recognition for both the radiologist (the results of computed tomography are non – specific), and for the attending physician (due to the poor clinical finding). Medullary sponge kidney is a benign congenital abnormality characterized by the formation of diffuse, bilateral medullary cysts caused by abnormalities in pericalyceal terminal collecting duct. The etiology is unknown, but in approximately 5 % of cases there is a genetic predisposition, according to the autosomal dominant type of inheritance. Literature review and a case study of medullary sponge kidney are presented. CT urography is one of the methods of choice in this pathology, and its value is especially great in recognizing the causes of complications of the disease, such as nephrolithiasis and macrohematuria. Purpose: to increase the awareness of practicing radiologists about CT signs of medullary spongy kidney. Material and methods: the data from the literature, as well as our own observation of the developmental abnormality – medullary spongy kidney – are presented. Results: CT scan capabilities in the diagnosis of medullary spongy kidney are described. Conclusion: CT is not the only, but an important method of diagnosis of medullary spongy kidney and knowledge of its pathophysiology and radiological manifestations will allow to make a correct diagnosis in time and prescribe the appropriate treatment.

Darier's follicular dyskeratosis

Darier's follicular dyskeratosis (synonym: Dariers disease, DarierWhites disease) is a rare genetic disease with an autosomal dominant type of inheritance, which belongs to the group of acantholytic dermatoses and is characterized by a violation of keratinization processes with lesions of the skin, nails, mucous membranes of the oral cavity and genitals. Dariers disease is caused by a mutation in the ATP2A2 gene. This disrupts the operation of the SERCA2 pump and leads to a violation of calcium homeostasis in keratinocytes and a decrease in intercellular adhesion. Dariers disease is manifested by brownish papules in seborrheic and intertriginal areas with a keratotic surface, which can merge into macerated plaques. Typical nail changes in Dariers disease include red and white longitudinal stripes ending in V-shaped notches on the free edge of the nail plates. Warty acrokeratosis, as well as bullous, hemorrhagic, comedonic and linear-segmental types are clinical variants of Dariers disease. Dariers disease is often associated with neuropsychiatric disorders. Exacerbation may be caused by superinfection with Staphylococcus aureus or by herpes simplex virus. Histology in Darieres disease is characterized by pronounced dyskeratosis. For local therapy, keratolytic agents are important, as well as antiseptic treatment to avoid superinfection. In addition, local corticosteroids are used. Among the systemic methods of treatment, the systemic retinoids are the most effective. Ablative methods of treatment (dermabrasion, CO2 laser, Er:YAG laser) are effective in limited areas.

ОСОБЕННОСТИ ДИАГНОСТИКИ И ЛЕЧЕНИЯ ГИГАНТСКОЙ АНГИОМИОЛИПОМЫ ПОЧКИ (КЛИНИЧЕСКИЙ СЛУЧАЙ)

Introduction. One of the rare complex diseases in clinical practice is Bourneville-Pringle disease (tuberous sclerosis). It is a genetically determined polysystemic disease with an autosomal dominant type of inheritance, one of the manifestations of which are renal angiomyolipomas. Angiomyolipoma is a benign kidney tumor. It consists of epithelioid, smooth muscle cells and adipose tissue and has abundant abnormal vascularization. Aim. We analyze a complex clinical case in a patient with a giant angiomyolipoma of a single kidney. Material and methods. Patient S., 58 years old, was urgently admitted to the urology department. The patient complained of pain in the left lumbar region, in the left half of the abdomen, blood impurities in the urine. General clinical, laboratory and instrumental research tools were conducted. Results and discussion. According to the spiral CT of the kidneys with contrasting, in the left kidney a giant mass with a violation of its architectonics, with signs of hemorrhage and a formed hematoma in the upper third of the mass and hemorrhagic impregnation of its lower half was found. Surgical treatment was prescribed, during which embolization of the segmental arteries of the left kidney, selective angiography of the left renal artery, total nephrectomy on the left with a successful outcome were performed. Conclusion. On the basis of the given clinical case, it should be concluded that despite the benign nature of the renal angiomyolipoma, the tumor has reached gigantic sizes due to the late treatment of the patient caused by concomitant oligophrenia. In this regard, the late diagnosis has led to life-threatening complications that required immediate decision-making. The given clinical observation shows the success of the chosen surgical tactics in the form of a radical operation that allowed saving the life of the patient with a rare disease. The patient was discharged from the hospital for outpatient follow-up by an urologist and a nephrologist. Regular hemodialysis, monitoring with the help of laboratory and instrumental research tools are prescribed. The patient was put on the waiting list for renal trans- plantation in specialized centers in Russia.

EPIDEMIOLOGICAL CHARACTERISTICS OF HEREDITARY MOTOR AND SENSORY NEUROPATHY IN THE KHARKOV REGION

Hereditary motor and sensory neuropathies are one of the most common diseases among monogenic hereditary diseases of the nervous system. Hereditary motor and sensory neuropathies are the group of clinically and genetically heterogeneous diseases characterized by peripheral nerve damage. Hereditary motor and sensory neuropathies have little effect on life expectancy, and this leads to their significant accumulation in individual families and in populations as a whole. The most common form of this disorder is hereditary motor and sensory neuropathy with an autosomal dominant type of inheritance - type 1A, caused by a mutation in the gene of peripheral myelin protein 22 (PMP22) on chromosome 17p11.2-12. According to various researches, the frequency of all hereditary motor and sensory neuropathies in the general population is 1:2500. The prevalence of hereditary motor and sensory neuropathies in different populations varies widely, therefore, the most appropriate at the initial stage of the genetic-epidemiological study of hereditary motor and sensory neuropathies is to determine the population frequency of this mutation in a specific region. The research of the territorial and ethnic distribution of hereditary motor and sensory neuropathies in the Kharkiv region was not carried out. That is why the aim of the research was to study and analyze the prevalence rates of hereditary motor and sensory neuropathies in the Kharkiv region in the context of administrative and territorial units and individual ethnic groups of the population. The epidemiological study of hereditary motor and sensory neuropathies in the Kharkiv region was carried out in the period from 2015 to 2020. The diagnosis of hereditary motor and sensory neuropathy was established in accordance with the recommendations of the WHO Research Group on neuromuscular diseases on the basis of diagnostic criteria.The prevalence rate of hereditary motor and sensory neuropathy was calculated both for various administrative and territorial units of the Kharkiv region and for individual ethnic groups of the population and expressed as the number of cases per 100,000 people. The results of the research showed that the prevalence rate of all forms of hereditary motor and sensory neuropathies in the Kharkiv region is 5.56 per 100,000 population and this indicator is unevenly distributed. The reason for the uneven distribution of hereditary motor and sensory neuropathies in the Kharkiv region may be the "effect of small samples" due to differences in population size both in individual administrative regions and in some ethnic groups of the population. In the Kharkiv region, the part of registered patients with hereditary motor and sensory neuropathies among the urban population (55.3%) is higher than among residents of country areas (44.7%). The heterogeneity of the prevalence rate of hereditary motor and sensory neuropathies in various ethnic groups of the Kharkiv region is due to the non-representativeness of these groups to the corresponding ethnic populations and such indicators cannot be transferred to the entire population as a whole. The high prevalence of hereditary motor and sensory neuropathies among certain ethnic groups is most likely due to the presence of ethnic isolates with a high degree of inbred members of the group.

Targeted exome analysis of Russian patients with hypertrophic cardiomyopathy.

BackgroundHypertrophic cardiomyopathy (HCM), described as the presence of hypertrophy of left ventricular, is the most prevalent heritable cardiovascular disease with predominantly an autosomal dominant type of inheritance. However, pathogenic alleles are not identified in at least 25% of patients with HCM, and the spectrum of pathogenic variants that contribute to the development of HCM in Russia has not been fully described. Therefore, the goal of our study was to identify genetic variants associated with the etiopathogenesis of HCM in Russian patients.MethodsThe study cohort included 98 unrelated adult patients with HCM. We performed targeted exome sequencing, an analysis using various algorithms for prediction of the impact of variants on protein structure and the prediction of pathogenicity using ACMG Guidelines.ResultsThe frequency of pathogenic and likely pathogenic variants in all HCM‐related genes was 8% in our patients. We also identified 20 variants of uncertain significance in all HCM‐related genes.ConclusionsThe prevalence of individual pathogenic variants in HCM‐related genes in Russian population appears to be lower than in general European population, which could be explained by ethnic features of Russian population, age characteristics of our sample, or unidentified pathogenic variants in genes previously not linked with HCM.

MOLECULAR-GENETIC ASPECTS OF KABUKI MAKEUP SYNDROME. Review

Relevance. Kabuki Makeup Syndrome (KS) is a rare monogenic genetic disease characterized by multiple malformations. The phenotype includes specific facial features, skeletal and dermatoglyphic abnormalities, mental retardation, short stature. Most cases are associated with de novo mutations in the KMT2D and KMD6A genes. However, in 25% of patients with KS, the genetic basis remains unknown, which indicates the genetic heterogeneity of the disease and encourages further accumulation of clinical experience in KS. The article summarizes current data on the molecular geneticі aspects of the development of Kabuki Makeup Syndrome and describes its own clinical case of Kabuki Makeup Syndrome Type I.
 Objective: to summarize the data on modern molecular-genetic aspects of the development of Kabuki makeup syndrome on the example of a clinical case.
 Materials and methods. Analysis of scientific publications in the international electronic scientometric database Scopus, PubMed by keywords. Search depth – 15 years (2007-2021). The clinical case of Kabuki Makeup Syndrome from our own practice. Clinical and genealogical, molecular-genetic, cytogenetic, instrumental research methods.
 Results. According to current data, the development of Kabuki Makeup Syndrome is due to mutations in the KMT2D (MLL2) gene, which belongs to the genes that control embryogenesis. KMT2D functions as a promoter of the expression of other genes and the KDM6A gene; encodes a large multidomain protein that interacts with the SET1/COMPASS complex. KDM6A is a cofactor physically associated with the KMT2D-COMPASS complex and exhibits demethylase activity in histone 3. Gene mutations KMT2D and KDM6A associated with KS lead to a lack of functioning of the corresponding enzyme, which leads to impaired methylation of histones and active genes in many organs and tissues of the body. Depending on the type of mutation in the KMT2D and KMD6A genes, there are two types of Kabuki Makeup Syndrome. KS type 1 with autosomal dominant type of inheritance due to pathogenic mutations in the KMT2D gene in a heterozygous state on chromosome 12q13.12. 70% of patients have KS1. Type 2 KS is an X-linked disease that develops as a result of a heterozygous pathogenic mutation in the KDM6 gene. In most cases, KS mutations are sporadic, but families with parent-to-child transmission have been described. In patients with phenotypic signs of KS pathogenic mutations are detected in 75% of cases. Pathogenic mutations in the KMT2D gene can be detected in mosaic form, and the carrier can pass this mutation on to offspring. Pathogenic mutations have not been described in phenotypically healthy people.
 Here is our own observation. The girl with a combined congenital heart defect and multiple stigmas of dysembryogenesis was born at 36 weeks with a weight of 2930, 49 cm long, on the Apgar scale 8/8 points from the third planned pregnancy in parents who already had an older healthy boy. In connection with multiple malformations, the girl underwent a syndromic diagnosis using the program "Face2gene"; Kabuki Makeup Syndrome is suspected. Molecular genetic analysis revealed a pathogenic mutation (c.11884C>T) (p.Gln3962*) in the KMT2D gene, which is associated with autosomal dominant Kabuki Makeup Syndrome of type 1 (MedGen UID: 893727).
 Conclusions. Kabuki Makeup Syndrome has clinical and molecular polymorphisms. Most of the registered KMT2D mutations occur de novo and occur in episodic cases. The described case demonstrates the molecular-positive Kabuki Makeup Syndrome of type I. The identified variant c.11884C>T(p.Gln3962*) in the KMT2D gene is associated with the autosomal dominant Kabuki Makeup Syndrome (MedGen UID: 893727). Verification of the diagnosis of the disease and prevention of KS in siblings is based on the results of molecular genetic analysis. The prognosis of this disease depends on the severity of heart disease and intellectual impairment. Early diagnosis determines the type and timing of therapeutic interventions, is crucial for medical and genetic counseling of the family.