[Pituitary disorders in patients with end-stage chronic renal failure].

Disorders in the kidneys lead to disturbance of homeostasis. As the glomerular filtration rate decreases, the metabolism of numerous biologically active substances, including pituitary hormones, decreases. The article presents an overview of pituitary dysfunction in patients with chronic kidney disease (CKD) and discusses the possible reasons of the pathogenetic mechanisms. Particular focus is being given to the assessment of changes in the concentration of pituitary hormones in patients with end-stage chronic kidney disease (CKD) and discusses the pathogenetic mechanisms of their formation. Particular attention is paid to the assessment of changes in the concentration of pituitary hormones in patients receiving renal replacement therapy (RRT). CKD leads to an increase in the level of prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Concentrations of growth hormone (GH), isulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and vasopressin may remain within normal values or increase in this group of patients. RRT does not reduce the levels of prolactin, LH, FSH, while the concentration of growth hormone, IGF-1, TSH tends to normalize. The content of ACTH and vasopressin may remain unchanged or decrease. Kidney transplantation in most cases corrects hormonal disorders. Correction of hormonal changes can improve the clinical outcome and quality of life of patients with end stage CKD.

The molecular complexity of COL2A1 splicing variants and their significance in phenotype severity.

Pathogenic single nucleotide variants (SNVs) found in the COL2A1 gene are associated with a broad range of skeletal dysplasias due to their impact on the structure and function of the Col2a1 protein. However, the molecular mechanisms of some nucleotide variants detected during diagnostic testing remain unclear. The interpretation of missense and splicing variants caused by SNVs poses a significant challenge for clinicians. In this work, we analyzed 22 splicing variants in the COL2A1 gene which have been found in patients with COL2A1-associated skeletal dysplasias. Using a minigene system, we investigated the impact of these SNVs on splicing and gained insights into their molecular mechanisms and genotype-phenotype correlations for each patient. The results of our study are very useful for improving the accuracy of diagnosis and the management of patients with skeletal dysplasias caused by SNVs in the COL2A1 gene.

Early audiological phenotype in patients with mutations in the USH2A gene.

INTRODUCTION: Nowadays, due to universal newborn hearing screening (UNHS) the number of children with mild-to-moderate hearing loss diagnosed in the first year of life has increased significantly. Aside from that, identification of the genetic cause improves the genetic counselling of the families and allows to reveal possible comorbidities which may need a special approach. OBJECTIVE: To present the characteristics of the early audiologic phenotype in hearing impaired patients with biallelic mutations in the USH2A gene based on systematic analysis of the audiological data. PATIENTS AND METHODS: 13 patients with mutations in the USH2A gene underwent audiological examination. Most of them were found among a large group of infants with bilateral nonsyndromic sensorineural hearing loss (SNHL) examined under 12 months. RESULTS: Eight out of eleven children failed UNHS and were initially diagnosed as having bilateral nonsyndromic SNHL. Seven children underwent an audiological assessment before the age of 9 months. The earliest audiological examination was carried out at 1 and 3 months. The children with pathogenic variants in the USH2A gene in our examined group were identified in the first year of life via UNHS. The hearing threshold levels (HTL) for the USH2A group are compactly distributed between 51.25 dB and 66.25 dB, quartiles are 54 dB and 63.4 dB, with a median of 60 dB. The audiological profile of patients with biallelic USH2A mutations differs from audiograms of patients who had STRC-related hearing loss. We have not found any significant elevation in hearing thresholds in the first decade of life. We also estimated the prevalence of the USH2A and STRC mutations among GJB2-negative infants with bilateral nonsyndromic SNHL examined under 12 months, and it was 7.5% and 16.1%, respectively. CONCLUSION: According to our results, the early hearing phenotype in pediatric patients with biallelic mutations in the USH2A- gene is characterized by nonsyndromic mild-to-moderate SNHL in the first decade of life. Our results indicate that the presence of mutations in the USH2A or STRC genes can be expected in a child with congenital mild-to-moderate nonsyndromic SNHL. This information is of practical importance for parents, as they have to know the prognosis of hearing loss for their child from the very beginning. Post-screening follow-up should include adequate clinical, genetic, and social support for children and their parents.

[Hearing loss due to mutations in the genes responsible for Usher syndrome]. / Narushenie slukha pri mutatsiyakh v genakh, otvetstvennykh za sindrom Ashera.

Usher syndrome is characterized by congenital bilateral sensorineural hearing loss and progressive retinitis pigmentosa, and has an autosomal recessive type of inheritance. The purpose of this work is to summarize the modern data of a clinical picture of Usher syndrome and analyse hearing impairment properties. The frequency of the syndrome among children suffering from hearing loss and deafness is from 3 to 10%. The prevalence of the syndrome in the world is estimated as 4.4 per 100.000 population. The complexity of the diagnosis of the syndrome lies in the significant clinical and genetic heterogeneity. Hearing and vision problems begin at different ages. Primary diagnosis begins with the clinical diagnosis of bilateral hearing loss and visual impairment manifests later. In this case the initial diagnosis of nonsyndromal hearing loss will not be definitive. Molecular genetic studies contribute to the early clinical diagnosis of the syndrome. Understanding the cause of the disease allows to conduct correct medical and genetic counseling and get closer to solving treatment problems.

[Ethical analysis of work environment in audiology]. / Analiz eticheskikh aspektov trudovoi deyatel'nosti vrachei-surdologov-otorinolaringologov i vrachei-otorinolaringologov.

The issues of medical ethics concern not only the doctor-patient relationship, but also the ethical aspects of the organization of the labor activity of medical specialists. Identifying and resolving ethical dilemmas can serve as the basis for preventing occupational stress and burnout and improving the effectiveness of medical care in the field of audiology. OBJECTIVE: Ethical analysis of work environment in audiology. MATERIAL AND METHODS: A 14-question questionnaire developed on the basis of demand-control and effort-reward models, an online survey was conducted using the Google Forms service among 111 specialists (43 audiologists, 13 otorhinolaryngologists, and 55 doctors combining work in both specialties).Results and discussion. The differences were revealed on the scales Effort and Reward depending on the specialty and clinic (public or private). The greatest effort was found among doctors combining both specialties, the least - among doctors of private clinics. 58% of the respondents consider the wages to be inadequate to the expended efforts. At the same time, a high respect level among patients, management and colleagues helps to compensate for the identified efforts. CONCLUSION: The analysis made it possible to identify ethical dilemmas in the work of audiologists for effective planning of specialty development.

[Adipocytokines: modern definition, classification and physiological role].

Adipose tissue is an endocrine organ which produces a large number of secretory bioactive substances also known as adipocytokines affecting directly insulin resistance (IR), glucose and lipid metabolism, angiogenesis and inflammation. The studies show a close connection between the imbalance of adipocytokines formed as a result of excessive deposit of adipose tissue in the course of the development of type 2 diabetes mellitus and cardiovascular diseases. In the present review, we summarize current data on the effect of the adipocytokines on the liver, skeletal muscles, adipose tissue, endothelial cells and inflammatory processes, as well as attempt to define the term «adipocytokines¼ and classify adipocytokines according to their influence on metabolic processes and pro-inflammatory status. Some of adipocytokines (adiponectin, omentin, leptin, resistin, tumor necrosis factor-α and interleukin-6) are divided into two groups: adipocytokines reducing IR, and adipocytokines increasing IR.

KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families.

BACKGROUND: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population. METHODS: Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel 'spastic paraplegias' with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing. RESULTS: AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. All 4 complicated cases were caused by novel mutations without familial history. The phenotypes varied from severe in two patients (e.g. lack of walking, pronounced mental retardation) to relatively mild non-disabling symptoms in two others. CONCLUSION: AD SPG30 is one of the most common forms of SPG in Russia, the disorder has pronounced clinical variability while pure familial cases represent a significant part.

Clinical features of hearing loss caused by STRC gene deletions/mutations in Russian population.

Congenital sensorineural hearing loss is related to mutations in numerous genes encoding the structures of the inner ear in majority of the cases. Mutations in GJB2 gene are the most frequently identified causes of congenital nonsyndromal hearing loss. GJB2 gene testing became a routine clinical tool. For GJB2-negative patients new genetic approaches including methods based on new generation sequencing give a chance to identify mutations in other genes. The frequent reason of mild-to-moderate hearing loss such as the deletions/mutations of the gene STRC encoding stereocilin protein were recognized (OMIM: 606440). OBJECTIVES: To evaluate the audiological features in hearing impaired patients with deletions and point mutations in the STRC gene. PATIENTS AND METHODS: The group of 28 patients from 21 unrelated families with pathological mutations in the STRC gene underwent audiological examination. The description and analysis of the results of full audiological examination was provided. RESULTS: All patients initially had bilateral nonsyndromal sensorineural hearing loss. Among 11 homozygotes of large deletion harboring STRC to CATSPER2 genes were 7 male individuals indicating the presence of male infertility syndrome. In general, 7 children failed audiological screening and 4 children underwent audiological assessment in the age of 3 and 6 months. The most frequently hearing thresholds were registered between 35 and 55 dB that corresponds to mild-to-moderate hearing impairment. The average age of diagnostics was 7.9 years (ranged from 3 months to 45 years). In the majority of patients the audiological profiles were flat or descending with elevation of thresholds at middle and high frequencies and relatively preserved thresholds at low frequencies. Hearing thresholds are symmetric and stable with age. CONCLUSION: STRC-linked hearing loss is congenital, of mild and moderate severity. Special clinical and genetic approach for children who failed newborn hearing screening with mild-to-moderate hearing loss is necessary.

[Hearing loss due to mutations or lack of the gene coding protein stereocillin]. / Narushenie slukha pri mutatsiyakh ili otsutstvii gena, kodiruyushchego belok stereotsilin.

OBJECTIVE: The description of a clinical picture and audiological features at the hearing loss caused by changes of a STRC gene, coding protein stereocillin (MIM: 606440). Mutations in the numerous genes responsible for the inner ear proteins are the reason for congenital sensorineural hearing loss. The main cause of congenital bilateral sensorineural hearing loss in the Russian Federation are mutations in GJB2 gene it reaches up 68% of cases identified in infancy. GJB2 gene tests already became routine around the world. Possibilities of new methods based on sequencing of new generation (NGS, next generation sequencing) allow to conduct a research of more rare genes connected with a hearing impairment. The most often among GJB2 negative patients reveal mutations and deletion of a gene of STRC. PATIENTS AND METHODS: Full audiological examination of 5 children and one adult with a hearing loss from 2 unrelated families is provided. Mutations in STRC gene were identified. All children are examined aged before 8 years, and 3 children failed universal audiological screening in maternity hospital, to two children screening was not carried out as they were born till 2009. RESULTS: The children with the sensorineural hearing loss connected with mutations and deletion of STRC gene failed hearing screening in maternity hospital because of the OAE is not registered, what indicates the congenital nature of a hearing loss. Recently it could not be noticed earlier because of slight increase of hearing thresholds and was regarded only as the early onset. Our data emphasize that the of thresholds from 35 to 60 dB in frequencies 0,5-4 kHz is common for mutations/deletions of STRC gene. CONCLUSION: The development of molecular genetics methods confirms the hereditary causes of GJB2-negative patients and expands indications for family counseling. Special approach for child with hearing loss so early revealed is necessary and the consultation of parents frightened of screening results is very important.

[OTOF-related auditory neuropathy spectrum disorder]. / Zabolevanie spektra auditornykh neiropatii, obuslovlennoe mutatsiyami v gene otoferlina (OTOF).

Otoferlin (OTOF) gene mutations are the most common cause of hereditary ANSD according to investigations in several countries. THE AIM: Of this study was to estimate the prevalence of OTOF mutations in Russian children with ANSD and evaluate audiological and clinical features of OTOF-related ANSD. PATIENTS AND METHODS: 28 children with bilateral ANSDwere enrolled in the investigation. Two step genetic testing was performed: first step - GJB2 gene testing to exclude GJB2-related hearing loss; second step - NGS-based sequencing to explore another 35 hearing loss genes (including OTOF). RESULTS: OTOF mutations, including 6 new variants, were found in 5 children with ANSD (18%). All 5 children had no risk factors for hearing loss and passed hearing screening. OAE and cochlear microphonics were present till the last testing at the age of 4-5 years. ABR were not detectable. The ASSR were measurable bilaterally at all frequencies in all cases, but they did not correlate with behavioral thresholds that revealed severe hearing loss. Hearing thresholds were stable during follow up period. 3 children underwent cochlear implantation. After cochlear implantation auditory nerve action potentials to electric stimulation were detected within normal range. CONCLUSION: Genetic testing of children with ANSD and first of all OTOF testing enables to reveal hearing loss etiology and provide the optimal rehabilitation approach, including cochlear implantation, as early as possible.

[Resolution on the results of the first working meeting of the Scientific Advisory Board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy¼].

June 19, 2018 the meeting of the Scientific Advisory Board took place in Moscow, chaired by Professor G.R. Galstyan, (co-chair - A.V. Zilov) devoted to the discussion of the possibilities of improving the results of treatment of diabetes mellitus (DM) by consideration of «variability of glycemia¼ (VG) as an additional criterion of the glycemic control effectiveness (especially of insulin therapy) as well as one of the goals of treatment in patients with unstable glycemia. The purpose of the working meeting was to develop a strategy for the introduction of VG as a predictor and an additional criterion in assessing the effectiveness and safety of hypoglycemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality. Aims: - to conduct a comprehensive data analysis of the relationship between VG and adverse DM outcomes, such as hypoglycemia, micro-and macrovascular complications, cardiovascular and total mortality; - to accumulate and analyze published data and the experience of decrease of VG and improving outcomes of diabetes on the background of different versions of insulin therapy; - to compare existing methods of glycaemia monitoring and VG assessment, their validity and availability in real practice in the context of limited budget; - to analyze the informativeness, clinical and prognostic significance of various parameters of VG assessment and determine their reasonable «minimum¼ for a comprehensive assessment of VG as a criterion for evaluating the effectiveness of treatment of DM and predictors of negative diabetes outcomes. The following reports were heard during the discussion: Glycemic variability: clinical and prognostic value. Types of glycemic variability. (Alexey V. Zilov, MD, PhD in Medicine, Assistant Professor). Methods of assessment of variability of glycemia in clinical trials and routine practice (Tatiana N. Markova, MD, PhD in Medicine, Professor). Current international and national recommendations on glycemic monitoring (Gagik R. Galstyan, MD, PhD in Medicine, Professor). Peculiarities of glycemic variability and its evaluation among children and adolescents (Alisa V. Vitebskaya, MD, PhD in Medicine).

[Analysis of cardiovascular safety of novel glucose-lowering medications].

In 2008 the Food and Drug Administration has revised approval process for new antidiabetic agents and introduced a requirement to demonstrate the cardiovascular safety in an international multicenter trial. Currently cardiovascular outcome trials of dipeptidyl peptidase-4 (DPP-4) inhibitors (SAVOR-TIMI53, EXAMINE and TECOS), sodium-glucose cotransporter 2 inhibitors (EMPAREG, CANVAS), glucagon-like peptide-1 receptor agonists (ELIXA, EXSCEL LEADER and SUSTAIN-6), ultralong-acting and insulin (DEVOTE) have been completed. The trials confirmed cardiovascular safety of these glucose-lowering medications, and in addition, EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin) and LEADER (liraglutide) have also demonstrated cardioprotective effect of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. These data led to the changes of clinical guidelines for the management of type 2 diabetes.

[Twenty years of clinical studies of GJB2-linked hearing loss in Russia]. / 20 let izucheniia klinicheskikh proiavlenii GJB2-obuslovlennoi tugoukhosti v Rossii.

The most common cause of congenital hereditary hearing loss was discovered 20 years ago in 1997 when GJB2 gene was revealed in the first locus of recessive hearing loss DFNB1. It encodes protein connexin 26, a structural component of the intercellular channels. Recessive mutations in this gene cause the congenital bilateral sensorineural hearing loss. For many years the aim of our work was to study the prevalence and clinical manifestations of hereditary hearing loss. Our research can be divided into three stages. In the beginning, we investigated the prevalence of GJB2 mutations in a healthy population and in the people suffering from hearing impairment. Further research was conducted in the field of clinical manifestations and evidence of the congenital character of GJB2-related hearing loss. Currently, we are working on the prevalence of mild and moderate hereditary hearing loss and the probability of its progression. Achievements in molecular genetics make it possible to establish the hereditary character of congenital hearing loss and to avoid repeated family cases. Primary prevention of hereditary hearing loss becomes real by raising the awareness of GJB2 mutations carriers.

[Epidemiology of hearing loss in children of the first year of life]. / Épidemiologiia narushenii slukha sredi detei 1-go goda zhizni.

The aim of this study was the investigation of the epidemiology of permanent hearing impairment in the children of first year of life in the Russian Federation after the implementation of the newborn universal hearing screening program. The prevalence of hearing loss in children in the first year of life was estimated at 2.5 per 1,000 based on the official statistical data and reports of hearing rehabilitation centres in 2016. A cohort of 405 children born in 2012 was examined at the age from 0 to 4 years of life. Among them 276 children were diagnosed with permanent congenital and prelingual hearing loss. 88% of the cases were bilateral, sensorineural hearing loss confirmed in 84% of the cases. The genetic cause of hearing loss was revealed in 58% of the patients assessed for the presence of GJB2 gene mutations. In preterm infants, the permanent hearing loss was detected in 70% of the cases. The comprehensive audiological assessment before 3 months of life was conducted only in 32% of the children; this finding is not consistent with the international newborn hearing screening recommendations. Only 70% of the cases of congenital and preverbal hearing loss were diagnosed during the first year of life.

[The analysis of the association of the polymorphic variants of the TPMT, COMT, and ABCC3 genes with the development of hearing disorders induced by the cisplatin treatment]. / Analiz assotsiatsii polimorfnykh variantov genov TPMT, COMT i ABCC3 c razvitiem narusheniia slukha, indutsirovannogo priemom tsisplatina.

Cisplatin and its derivatives are widely used chemotherapeutic agents for the treatment of many cancers, including hepatoblastoma, brain tumors, and germ-cell tumors. This therapy contributed to the dramatic increase in the survival rate. However, its use is restricted by the high incidence of irreversible ototoxicity associated with cisplatin application (in more than 60% of the children receiving it). Some studies have reported that genetic variants of TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) are conferring increased risk of developing cisplatin-induced hearing loss. However, in other studies the results were not replicated. In the present study, we replicated the previous studies based on an independent cohort of Russian patients. SNP genotypes for rs 12201199, rs4646316 and rs 1051640 were determined in DNA samples obtained from 16 patients who developed hearing loss and a group of 34 patients whose hearing was retained. The association between TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) variants and the hearing loss was not observed in our cohort.

[Results of molecular genetic testing in Russian patients with Pendred syndrome and allelic disorders].

Pendred syndrome is an autosomal recessive inherited disorder characterized by a combination of sensorineural hearing impairment and euthyroid goiter; its clinical manifestation in children is hardly distinguishable from nonsyndromic hearing loss. Pendred syndrome is one of the most frequent types of syndromic hearing loss. Hearing impairment is accompanied by abnormal development of the bony labyrinth­enlarged vestibular aqueduct (EVA) and occasionally combined with Mondini dysplasia. Mutations in the SLC26A4 gene, which encodes the pendrin protein, are responsible for both Pendred syndrome and for allelic disorder (nonsyndromic enlarged vestibular aqueduct). The present study for the first time conducted molecular genetic analysis in 20 Russian patients with Pendred syndrome, EVA and/or Mondini dysplasia. As a result, six pathogenic mutations in the SLC26A4 gene were revealed in four patients. The mutation c.222G>T (p.Trp74Cys) was detected for the first time. Mutations were found in patients with Pendred syndrome and nonsyndromic EVA with or without Mondini dysplasia. Mutations were not detected in patients with isolated Mondini dysplasia. One proband with clinical diagnosis Pendred syndrome was homozygous for the c.35delG mutation in the GJB2 gene. The absence of frequent mutations, including well-known ones or "hot" exons in the SLC26A4 gene, was reported. Therefore, the optimal method to search for mutations in the SLC26A4 gene in Russian patients is Sanger sequencing of all exons and exon-intron boundaries in the SLC26A4 gene.

[The Russian and international experience with the implementation of the programs of universal audiological screening of the newborn infants].

The problem of diagnostics of congenital hearing impairment has acquired special importance in the light of new possibilities for the early rehabilitation of the patients presenting with this condition. The implementation of the programs of universal audiological screening into the clinical practice of Russia and many other countries made it possible to significantly reducethe time necessary to confirm congenital impairment of hearing and begin the rehabilitative treatment. The present paper was designed to analyze the international experience with the implementation of the programs of universal audiological screening of the newborn infants as exemplified by such countries as Great Britain, USA, Germany, and Poland. The main indicators of the quality and the efficiency of such programs are considered taking into account the results of the epidemiological studies on the prevalence of congenital hearing impairment. A total of 1.8 mln newborn infants were examined in Russia during 2013. The first stage of screening involved 96.7% of the children, and only 2.9% of them remained uncovered by the examination. As many as 5,659 children were found to present with the congenital loss of hearing,with the prevalence of this condition being 3 per 1.000 newborn infants and the prevalence of deafness 0.6 per 1.000. The principal problem to be resolved for the organization of the management of these patients, both in Russia and other countries, remains the enhancement of the availability of comprehensive diagnostic examination and the timelyreferral of the patients to such examination (if appropriate based on the results of the screening). The successful solution of this problem requires personalized recording of the screening data with the use of the commonly accepted medical information systems.

Phenotype in a patient with p.D50N mutation in GJB2 gene resemble both KID and Clouston syndromes.

Keratitis-ichthyosis-deafness (KID) syndrome (OMIM 148210) is a rare ectodermal dysplasia syndrome characterized by vascularizing keratitis, congenital profound sensorineural hearing loss, and progressive erythrokeratoderma. We have found a 148G-A transition in the GJB2 gene, resulting in an asp50-to-asn (D50N) substitution in a girl with congenital deafness. This finding allowed us to diagnose а KID syndrome. But clinical features were uncommon because of a mild skin manifestation, lack of keratitis and unusual appearance resembling Clouston syndrome. Molecular genetic tests showed that it was de novo mutation because parents have normal genotype. Several autosomal dominant mutations in the GJB2 gene (сonnexin 26) now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. Skin disease-associated mutation of connexin proteins can cause functional disturbances in gap junction intercellular conductance. It is likely that multiple disease mechanisms are involved across the wide spectrum of hereditary diseases relating to connexin proteins. The clinical data may provide additional insights into the dysregulation mechanisms of mutations result in the disease.

[The results of cochlear implantation in the patient with hereditary and non-hereditary hearing loss]. / Rezul'taty kokhlearnoi implantatsii u patsientov s nasledstvennymi i nenasledstvennymi formami tugoukhosti.

The objective of the present study was to evaluate the effectiveness of rehabilitation of the patients after cochlear implantation in the early and late periods after operation taking into consideration the etiology of congenital deafness. The comprehensive clinico-audiological examination performed during the period from 2010 to 2015 involved 246 children who had undergone cochlear implantation (CI). All children were operated at the National Research Center for Audiology and Hearing Rehabilitation in the period from 2003 to 2013. 83 (56%) patients were aged 1 to 3 years at the time of surgery. Their age varied from 3 to 18 years when they underwent the clinico-audiological examination. Thus, the study is based on the experience with cochlear implantation varying from 3 to 12 years. The genetic analysis revealed mutations in the GJB2 gene in 49% of the children, in agreement with the data of earlier studies. 85% of all the children with GJB2 deafness surgically treated at the age under 4 years attend ordinary institutions of learning. Within 24 months after the onset of the observations the majority of the children with hereditary deafness (63%) were referred to the groups with good and excellent results of the rehabilitation and only 6 (12%) patients presented with unsatisfactory results. It was shown that the acquired causes of the loss of hearing including severe prenatal pathology have a negative influence on the long-term outcomes of rehabilitation. The results of the genetic analysis for the elucidation of the cause of impaired hearing can be employed as a prognostic criteria not only for the prediction but also for the guarantee of the success of cochlear implantation provided the rehabilitative process was initiated in a proper time.

[The clinical definition and etiology of Pendred syndrome (a review of the literature and clinical observations)]. / Sindrom Pendreda (obzor literatury i klinicheskie nablyudeniya).

The aim of this work was a clinical study of the patients with mutations in the SLC26A4 gene and clinical diagnosis of the Pendred syndrome. The Pendred syndrome is a hereditary autosomal recessive disorder characterized by combined pathology of the inner ear and the thyroid gland. CT of the temporal bones demonstrates the Mondini-type structural anomaly in the inner ear and enlarged vestibular aqueduct. Examination of the thyroid gland reveals hypothyroidism and euthyroid goiter. A total of 20 unrelated children at the age from 2 to 16 years presenting with the hearing loss of different severity were available for the examination. High-resolution CT of the temporal bones demonstrated abnormal development of the inner ear including the Mondini-type structural anomaly and enlarged vestibular aqueduct. Five children with congenital hypothyroidism suffered from bilateral sensorineural impairment of hearing. The routine methods of audiological and molecular genetic examination were used throughout the study. RESULTS: As a result of molecular genetic studies, four out of the 20 patients were found to carry six recessive mutations of the SLC26A4 gene in the compound heterozygous and one such gene in the homozygous state which confirmed the hereditary nature of the disease. The children suffered the hearing loss of varying severity diagnosed at different age. The thyroid hypofunction in one child was identified when it was 2 years of age, and in two children at the age of 8 and 9 years. CONCLUSION: The first step in the diagnosis of the Pendred syndrome among children with congenital hearing loss was a CT scan of the temporal bones that showed incomplete separation of the curls of the cochlea and enlarged vestibular aqueduct. It is necessary to continue to study epidemiology, clinical and molecular genetics of the Pendred syndrome in the Russian population.