Neoplastic potential for malformations of the development of ecto- and mesodermal structures

2020 ◽  
Vol 1 (4) ◽  
pp. 208-216
Author(s):  
Zhuzhuna M. Tsotsonava ◽  
Vladimir V. Belopasov ◽  
Natal’ya V. Tkacheva
Keyword(s):  
Nervous System ◽  
Abdominal Cavity ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Neurofibromatosis Type ◽  
Hereditary Diseases ◽  
Organ Specificity ◽  
Type Iv ◽  
Skin Blood Vessels

Introduction.Malformations of ecto- and mesodermal structures represent various forms of abnormality of intrauterine systemic and local morphogenesis, arising at different times of embryonic development due to environmental factors, genomic, chromosomal or gene mutations. Dysregulation of cellular functions due to mutations and accumulation of defective proteins initiates tumor transformation of tissues e.g. hereditary diseases of ectomesodermal origin phakomatosis (hamartomatosis). The aim of the studywas to determine organ specificity, clinical manifestations, morphological features and the degree of progression of tumors of the nervous system and internal organs in hereditary diseases of ectomesodermal origin. Materials and methods.103 patients with hereditary phakomatosis were examined. All of them underwent a comprehensive clinical imaging examination, including magnetic resonance imaging, echocardioscopy, ultrasound examination of the abdominal organs, kidneys, retroperitoneal space, and computed tomography of the abdominal cavity and lungs. Results.The reason for the treatment of patients was the occurrence of focal neurological symptoms, focal and/or generalized epileptic seizures. Clinical manifestations were determined by the form of the disease. The risk of the development and progression of various neoplasms is the highest in neurofibromatosis type III, tuberous sclerosis, neurocutaneous melanosis, multiple endocrine neoplasia, angiomatosis of HippelLindau, Louis-Bar . Favorable benign and stable course, low malignant potential are distinguishing characteristics of pigment-vascular phakomatoses type IV. Conclusion.Knowledge of the clinical manifestations of various malformations of the skin, blood vessels, and the nervous system associated with tumor growth in cells and tissues is practically significant. Early diagnosis and the use of modern technologies of conservative and surgical treatment allow achieving a predictable result, prevent the development of severe complications, and significantly improve the quality of life of patients with this pathology.

scholarly journals GENETIC DIAGNOSTICS AND CLINICAL FEATURES OF WILSON’S DISEASE IN CHILDREN

2020 ◽  
Vol 2 ◽  
pp. 3-9
Author(s):  
Ivanna Haiboniuk ◽  
Marta Dats-Opoka ◽  
Halyna Makukh ◽  
Yaryna Boyko ◽  
Igor Kiselyk
Keyword(s):  
Nervous System ◽  
Genetic Analysis ◽  
Wilson’S Disease ◽  
Clinical Manifestations ◽  
Wilson's Disease ◽  
Hereditary Diseases ◽  
Genetic Diagnostics ◽  
Atp7b Gene ◽  
Hepatobiliary System ◽  
Child Age

A disorder of copper metabolism at Wilson’s disease (WD), conditioned by a mutation of adenosine thriphospate P-type gene (ATP7B), results in irreversible changes in the liver and in the nervous system. Mortality is high at WD, but it is one of hereditary diseases, well subjected to the therapy. The disease is manifested in the early age, but its clinical course in children is symptomless that essentially complicates diagnostics. A single reliable method is genetic analysis for revealing mutations in ATP7B gene. The aim of the work was to analyze clinical manifestations and course of Wilson’s disease cases, genetically verified in children by detecting mutations of ATP7B gene. The research group included children of 6-17 years old with different injury degrees of the hepatobiliary system. According to results of the molecular-genetic analysis, the most spread allele variant of ATP7B gene (H1069Q) in Europe was confirmed in 10 patients of child age, including 4 cases of homozygosity. In 10 cases of the confirmed diagnosis of Wilson’s disease in child age in 100% (in all 10) of persons, a clinical manifestation was characterized by disorders from the hepatobiliary system, and only in 1 (10 %) – changes from the nervous system. At raising the level of transaminase in children, even at the normal bilirubin level and negative tests for viral hepatitis, it is recommended to carry out genetic testing for Wilson’s disease

scholarly journals PREGABALINS IN THE MANAGEMENT OF DIABETIC AND ALCOHOLIC POLYNEUROPATHY

2021 ◽  
Vol 21 (2) ◽  
pp. 24-27
Author(s):  
N.V. Vasylieva ◽  
I.I. Krychun
Keyword(s):  
Nervous System ◽  
Severe Disease ◽  
Late Complication ◽  
Conduction Block ◽  
Clinical Manifestations ◽  
Diabetic Polyneuropathy ◽  
Hereditary Diseases ◽  
Motor Impairments ◽  
Developmental Patterns ◽  
Leading Position

Diseases of the peripheral nervous system are ranking a leading position among other neurological nosologies. And polyneuropathy is known as more prevalent and severe disease. Numerous scientific reports highlight issues on different pathological conditions in relation to polyneuropathy, and in particular intoxications, hypovitaminosis (isolated or as complications of certain pathological processes), infectious and hereditary diseases, paraneoplastic syndromes, metabolic disorders, allergic reactions. These diseases when uncontrolled or untreated may result in the development of complications, among which is polyneuropathy. The diagnosis of polyneuropathy is relatively not difficult, because the disease is manifested as distal symmetrical sensory and/or motor impairments with transient disorders of autonomic nervous system. Diabetic polyneuropathy, in particular, is a late complication of diabetes mellitus, which determines the prognosis of the disease. Alcoholic polyneuropathy in a form of acute, subacute or chronic current variants is caused by the combined effects of thiamine toxicity and vitamin deficiency. At the same time, dysmetabolic polyneuropathies differ by variability of clinical manifestations and the general developmental patterns of the nerve conduction block that is determined by the peculiarities of degenerative and regenerative processes under different pathogenetic factors. Differential diagnosis of polyneuropathies is mainly based on the detection of somatic pathology and the comparison of the dynamic changes in the course of the diseases and clinical manifestations. The study has demonstrated diabetic and alcoholic polyneuropathies have clear distinct clinical-neurophysiological patterns. The article also highlights the treatment outcomes of combination therapy with pregabalin for diabetic and alcoholic polyneuropathies.

scholarly journals Towards Central Nervous System Involvement in Adults with Hereditary Myopathies

2020 ◽  
Vol 7 (4) ◽  
pp. 367-393
Author(s):  
Jens Reimann ◽  
Cornelia Kornblum
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuromuscular Disorders ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Central Nervous System Involvement ◽  
Epileptic Seizures ◽  
System Involvement ◽  
History Of ◽  
Neuroimaging Techniques

There is increasing evidence of central nervous system involvement in numerous neuromuscular disorders primarily considered diseases of skeletal muscle. Our knowledge on cerebral affection in myopathies is expanding continuously due to a better understanding of the genetic background and underlying pathophysiological mechanisms. Intriguingly, there is a remarkable overlap of brain pathology in muscular diseases with pathomechanisms involved in neurodegenerative or neurodevelopmental disorders. A rapid progress in advanced neuroimaging techniques results in further detailed insight into structural and functional cerebral abnormalities. The spectrum of clinical manifestations is broad and includes movement disorders, neurovascular complications, paroxysmal neurological symptoms like migraine and epileptic seizures, but also behavioural abnormalities and cognitive dysfunction. Cerebral involvement implies a high socio-economic and personal burden in adult patients sometimes exceeding the everyday challenges associated with muscle weakness. It is especially important to clarify the nature and natural history of brain affection against the background of upcoming specific treatment regimen in hereditary myopathies that should address the brain as a secondary target. This review aims to highlight the character and extent of central nervous system involvement in patients with hereditary myopathies manifesting in adulthood, however also includes some childhood-onset diseases with brain abnormalities that transfer into adult neurological care.

scholarly journals PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Piero Pavone ◽  
Giovanni. Corsello ◽  
Sung Yoon Cho ◽  
Xena Giada Pappalardo ◽  
Martino Ruggieri ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Transmembrane Protein ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Dysmorphic Features ◽  
Severe Intellectual Disability ◽  
Infantile Epilepsy ◽  
Congenital Microcephaly

Abstract Background Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. Case presentation We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. Conclusion Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation.

scholarly journals Atypical NF1 Microdeletions: Challenges and Opportunities for Genotype/Phenotype Correlations in Patients with Large NF1 Deletions

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1639
Author(s):  
Hildegard Kehrer-Sawatzki ◽  
Ute Wahlländer ◽  
David N. Cooper ◽  
Victor-Felix Mautner
Keyword(s):  
Developmental Delay ◽  
Cognitive Abilities ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Global Developmental Delay ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Nf1 Gene

Patients with neurofibromatosis type 1 (NF1) and type 1 NF1 deletions often exhibit more severe clinical manifestations than patients with intragenic NF1 gene mutations, including facial dysmorphic features, overgrowth, severe global developmental delay, severe autistic symptoms and considerably reduced cognitive abilities, all of which are detectable from a very young age. Type 1 NF1 deletions encompass 1.4 Mb and are associated with the loss of 14 protein-coding genes, including NF1 and SUZ12. Atypical NF1 deletions, which do not encompass all 14 protein-coding genes located within the type 1 NF1 deletion region, have the potential to contribute to the delineation of the genotype/phenotype relationship in patients with NF1 microdeletions. Here, we review all atypical NF1 deletions reported to date as well as the clinical phenotype observed in the patients concerned. We compare these findings with those of a newly identified atypical NF1 deletion of 698 kb which, in addition to the NF1 gene, includes five genes located centromeric to NF1. The atypical NF1 deletion in this patient does not include the SUZ12 gene but does encompass CRLF3. Comparative analysis of such atypical NF1 deletions suggests that SUZ12 hemizygosity is likely to contribute significantly to the reduced cognitive abilities, severe global developmental delay and facial dysmorphisms observed in patients with type 1 NF1 deletions.

scholarly journals Clinical and genetic characteristics of new allele variants of the Mowat–Wilson syndrome caused by ZEB2 gene mutations

2018 ◽  
Vol 8 (3) ◽  
pp. 28-33
Author(s):  
I. A. Akimova ◽  
T. V. Markova ◽  
F. A. Konovalov ◽  
A. V. Antonets ◽  
E. L. Dadali
Keyword(s):  
Intellectual Development ◽  
Survey Methods ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Speech Development ◽  
Hereditary Diseases ◽  
Genetic Characteristics ◽  
Monogenic Diseases ◽  
Long Time ◽  
Nextgeneration Sequencing

To date, a large number of monogenic diseases and syndromes, in the clinical picture of which there are convulsions, a psycho-speech development delay and dysmorphic features have been described. One of the hereditary syndromes with a specific phenotype is the Movat–Wilson syndrome. To diagnose the syndrome, a set of survey methods was used: genealogical analysis, neurological examination, evaluation of intellectual development with the help of psychological tests, and sequencing of the new generation exome. As a result of sequencing exome on the panel of genes responsible for the emergence of hereditary epilepsy, two patients of different sex at the age of 10 and 5 years were identified with previously not described mutations in the ZEB2 gene in the heterozygous state. Clinical manifestations of the disease in these patients were of varying degrees of severity, which can be explained in terms of the functional significance of the changes detected. The variety of clinical manifestations of the same disease leads to considerable difficulties in diagnosing, however, due to the introduction of the nextgeneration sequencing in medical practice, the effectiveness of diagnosing hereditary diseases and syndromes, the verification of which has been difficult for a long time, has increased significantly.

scholarly journals Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

2020 ◽  
Vol 14 (3) ◽  
pp. 28-36
Author(s):  
E. L. Dadali ◽  
I. A. Akimova ◽  
F. A. Konovalov ◽  
P. A. Shatalov ◽  
A. Yu. Krasnenko ◽  
...  
Keyword(s):  
Genetic Variant ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Psychomotor Retardation ◽  
Dominant Inheritance ◽  
Common Genetic Variant ◽  
Genetic Characteristics

Early infantile epileptic encephalopathies (EIEE) are a group of disorders characterized by pharmacoresistant epileptic seizures manifesting in infancy and leading to psychomotor retardation. The most common genetic variant with X-linked dominant inheritance is type 2 EIEE associated with CDKL5 gene mutations. We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE. The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.

scholarly journals VARIETY OF CLINICAL MANIFESTATIONS IN MUTATIONS IN THE DYNC1H1 GENE

2019 ◽  
pp. 31-36
Author(s):  
I. V. Sharkova ◽  
P. A. Shatalov ◽  
E. L. Dadali
Keyword(s):  
Protein Function ◽  
Muscular Atrophy ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Hereditary Diseases ◽  
Clinical Markers ◽  
Tail Domain ◽  
Genetic Characteristics ◽  
Main Method ◽  
Brain Malformations

Introduction. To date, DYNC1H1 gene mutations are known for large number of hereditary diseases. It is believed that different mutations have variable effects to protein function and, accordingly, to various clinical manifestations. Results. There are a clinical and genetic characteristics of two Russian patients with two types of diseases: spinal muscular atrophy with predominant lesion of the lower extremities (SMALED) and non-syndromic mental retardation type 13 (MR13) in combination with a brain malformations and epilepsy due to newly identified mutations in the DYNC1H1 gene. Conclusion There is some evidence in support of the hypothesis that the amino acid sequence changing in the tail domain of dynein lead to the appearance of SMALED, and in the motor domain lead to MR13. Exome or genome sequencing are required as the main method for their diagnosis due to the high genetic heterogeneity of non-syndromic MR and SMALED, the lack of specific clinical markers and hotspot mutations in the DYNC1H1 gene.

Clinical Manifestations and Radiological Characteristics on Rosai-Dorfman Disease: A Retrospective Observational Study

2020 ◽  
Vol 5 (5) ◽  
Keyword(s):  
Blood Vessels ◽  
Abdominal Cavity ◽  
Clinical Manifestations ◽  
Ct Images ◽  
High Signal ◽  
Radiological Features ◽  
Imaging Characteristics ◽  
Rosai Dorfman Disease ◽  
Heterogeneous Enhancement ◽  
The Masses

Background and Objective: Rosai-Dorfman disease (RDD) are usually misdiagnosed because of rarity and nonspecific clinical and radiological features. The aim of our study is to explore the clinical and imaging characteristics of RDD to improve diagnostic accuracy. Methods: Clinical and imaging data in 10 patients with RDD were retrospectively analyzed. 7 patients were underwent CT scanning and 3 patients were underwent MR examination. Results: 8 (8/10) patients presented with painless enlarged lymph nodes (LNs) or mass. 3 cases were involved with LNs, 5 cases were involved with extra-nodal tissues, and the remaining 2 cases were involved with LNs and extra-nodal tissue simultaneously. In enhanced CT images, enlarged LNs displayed mild or moderate enhancement, and 2 cases showed heterogeneous ring-enhancement. MR features of 3 patients with extra-nodal RDD, 2 cases showed a mass located in the subcutaneous and anterior abdominal wall respectively, and 1 case showed an intracranial mass. Besides, all lesions showed high signal foci on DWI images, and were characterized by marked heterogeneous enhancement with blurred edge. The dural/fascia tail sign and dilated blood vessels could be seen around all the lesions on enhanced MRI. Radiological features of 2 cases with LN and extranodal tissue involved, one case presented with the swelling and thickening of pharyngeal lymphoid ring and nasopharynx, meanwhile with enlarged LNs in bilateral submandibular area, neck and abdominal cavity, and also companied with osteolytic lesion in right proximal humerus. All these LNs displayed mild and moderate enhancement on CT images. Another case showed enlarged LNs in bilateral neck accompanied with soft tissue mass in the sinuses. Conclusions: RDD occurred commonly in young and middle-aged men and presented with painless enlarged LNs or mass.RDD had a huge diversity of imaging findings, which varied with different location. The radiological features, such as small patches of high signal foci in the masses on DWI images, heterogeneous enhancement and blood vessels around the masses, are helpful in diagnosis of extranodal RDD.

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