scholarly journals Spinal and bulbar muscular atrophy as a multisystem disease with motor neuron and muscle involvement: literature review and a case report

2020 ◽  
Vol 10 (1) ◽  
pp. 81-87
Author(s):  
E. O. Ivanova ◽  
E. Yu. Fedotov ◽  
S. N. Illarioshkin
Keyword(s):  
Case Report ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Receptor Gene ◽  
Clinical Manifestations ◽  
Androgen Receptor Gene ◽  
Muscle Pathology ◽  
Multisystem Disease ◽  
Muscle Involvement ◽  
Polyglutamine Expansion

The spinal and bulbar muscular atrophy is a slowly progressive X-linked polysystemic disease associated with polyglutamine expansion in the androgen receptor gene. The mutant protein exhibits toxic properties towards neurons and myocytes. The main motor manifestations of the spinal and bulbar muscular atrophy are weakness, atrophy and fasciculation of the muscles of the limbs and bulbar group. Traditionally spinal and bulbar muscular atrophy belongs to the group of motor neuron diseases, but in recent years there is increasing evidence of a significant role of primary muscle pathology in the pathogenesis and clinical picture of this disease. This article provides a review of the literature on the pathogenesis, clinical manifestations and diagnosis of the spinal and bulbar muscular atrophy. We present a case report of the spinal and bulbar muscular atrophy with a clinical findings resembling metabolic myopathy.

scholarly journals Nucleic Acid-Based Therapeutic Approach for Spinal and Bulbar Muscular Atrophy and Related Neurological Disorders

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 109
Author(s):  
Tomoki Hirunagi ◽  
Kentaro Sahashi ◽  
Katherine G. Meilleur ◽  
Masahisa Katsuno
Keyword(s):  
Nucleic Acid ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neurological Disorders ◽  
Neurodegenerative Disorder ◽  
Muscular Atrophy ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Muscle Pathology ◽  
Small Interfering Rnas

The recent advances in nucleic acid therapeutics demonstrate the potential to treat hereditary neurological disorders by targeting their causative genes. Spinal and bulbar muscular atrophy (SBMA) is an X-linked and adult-onset neurodegenerative disorder caused by the expansion of trinucleotide cytosine-adenine-guanine repeats, which encodes a polyglutamine tract in the androgen receptor gene. SBMA belongs to the family of polyglutamine diseases, in which the use of nucleic acids for silencing a disease-causing gene, such as antisense oligonucleotides and small interfering RNAs, has been intensively studied in animal models and clinical trials. A unique feature of SBMA is that both motor neuron and skeletal muscle pathology contribute to disease manifestations, including progressive muscle weakness and atrophy. As both motor neurons and skeletal muscles can be therapeutic targets in SBMA, nucleic acid-based approaches for other motor neuron diseases and myopathies may further lead to the development of a treatment for SBMA. Here, we review studies of nucleic acid-based therapeutic approaches in SBMA and related neurological disorders and discuss current limitations and perspectives to apply these approaches to patients with SBMA.

scholarly journals Beyond motor neurons: expanding the clinical spectrum in Kennedy’s disease

2018 ◽  
Vol 89 (8) ◽  
pp. 808-812 ◽  
Author(s):  
Raquel Manzano ◽  
Gianni Sorarú ◽  
Christopher Grunseich ◽  
Pietro Fratta ◽  
Emanuela Zuccaro ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Multidisciplinary Approach ◽  
Muscular Atrophy ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Motor Neuron Degeneration ◽  
Kennedy’S Disease ◽  
Kennedy's Disease ◽  
Repeat Expansions

Kennedy’s disease, or spinal and bulbar muscular atrophy (SBMA), is an X-linked neuromuscular condition clinically characterised by weakness, atrophy and fasciculations of the limb and bulbar muscles, as a result of lower motor neuron degeneration. The disease is caused by an abnormally expanded triplet repeat expansions in the ubiquitously expressed androgen receptor gene, through mechanisms which are not entirely elucidated. Over the years studies from both humans and animal models have highlighted the involvement of cell populations other than motor neurons in SBMA, widening the disease phenotype. The most compelling aspect of these findings is their potential for therapeutic impact: muscle, for example, which is primarily affected in the disease, has been recently shown to represent a valid alternative target for therapy to motor neurons. In this review, we discuss the emerging study of the extra-motor neuron involvement in SBMA, which, besides increasingly pointing towards a multidisciplinary approach for affected patients, deepens our understanding of the pathogenic mechanisms and holds potential for providing new therapeutic targets for this disease.

scholarly journals X-linked spinal and bulbar muscular atrophy (Kennedy’s disease): the first case described in the Brazilian Amazon

2018 ◽  
Vol 16 (2) ◽  
Author(s):  
Camila Nascimento Alves ◽  
Tiago Kiyoshi Kitabayashi Braga ◽  
Danusa Neves Somensi ◽  
Bruno Sérgio Vilhena do Nascimento ◽  
José Antônio Santos de Lima ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Receptor Gene ◽  
Brazilian Amazon ◽  
Androgen Receptor Gene ◽  
Thoracic Spinal Cord ◽  
Kennedy’S Disease ◽  
Kennedy's Disease ◽  
First Case ◽  
Patient Reported

ABSTRACT The X-linked spinal and bulbar muscular atrophy (Kennedy’s disease) is a rare X-linked, recessive, lower motor neuron disease, characterized by weakness, atrophy, and fasciculations of the appendicular and bulbar muscle. The disease is caused by an expansion of the CAG repetition in the androgen receptor gene. Patients with Kennedy’s disease have more than 39 CAG repetitions. We report a case of 57-year-old man, resident of Monte Dourado (PA, Brazil) who complained of brachiocrural paresis evolving for 3 years along with fasciculations and tremors of extremities. In addition, he also developed dysarthria, dysphagia, and sexual dysfunction. The patient clinical picture included gait impairment, global hyporeflexia, proximal muscle atrophy of upper limbs, deviation of the uvula to right during phonation and tongue atrophy with fasciculations. The patient reported that about 30 years ago he had undergone gynecomastia surgery. His electroneuromyography suggested spinal muscular atrophy, and nuclear magnetic resonance imaging showed tapering of the cervical and thoracic spinal cord. Patient’s creatine kinase level was elevated. In view of the findings, an exam was requested to investigate Kennedy’s disease. The exam identified 46 CAG repetitions in the androgen receptor gene, which confirmed the diagnostic suspicion. This was the first case of Kennedy’s disease diagnosed and described in the Brazilian Amazon. To our knowledge only other four papers were published on this disease in Brazilian patients. A brief review is also provided on etiopathogenic, clinical and diagnostic aspects.

Pure bulbar motor neuron involvement linked to an abnormal CAG repeat expansion in the androgen receptor gene

2008 ◽  
Vol 9 (1) ◽  
pp. 40-42 ◽  
Author(s):  
Julien Praline ◽  
Anne‐Marie Guennoc ◽  
Marie‐Claire Malinge ◽  
Bertrand de Toffol ◽  
Philippe Corcia
Keyword(s):  
Androgen Receptor ◽  
Motor Neuron ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Repeat Expansion ◽  
Cag Repeat ◽  
Cag Repeat Expansion

scholarly journals Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
Hooi Ling Teoh ◽  
Kate Carey ◽  
Hugo Sampaio ◽  
David Mowat ◽  
Tony Roscioli ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Protein Quality ◽  
Neurodegenerative Disorder ◽  
Muscular Atrophy ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Next Generation ◽  
Generation Sequencing

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis.

scholarly journals A case of a 22-year-old man with primary synovial sarcoma of the parapharyngeal space with an AR somatic mutation: A case report and review of the literature

2022 ◽  
Vol 10 ◽  
pp. 2050313X2110686
Author(s):  
He Jiang ◽  
Ge Ma ◽  
Zunzhen Nie ◽  
Jin Zhu ◽  
Qingguo Yan ◽  
...  
Keyword(s):  
Case Report ◽  
Androgen Receptor ◽  
Somatic Mutations ◽  
Receptor Gene ◽  
Genetic Alterations ◽  
Androgen Receptor Gene ◽  
Tumour Cells ◽  
Novel Technologies ◽  
Spindle Cells ◽  
Body Sensation

This case report describes a 22-year-old man with a pharyngeal foreign body sensation arising from the left side of the postpharyngeal wall. Histological examination showed a biphasic pattern of epithelioid and spindle cells including glandular differentiation. The tumour was positive for vimentin and SS18-SSX, and the spindle cells were positive for bcl-2; in contrast, the epithelioid tumour cells were positive for pan-cytokeratin, epithelial membrane antigen and CD99. There was no INI-loss in tumour cells. Then, the presence of the SYT-SSX gene fusion was demonstrated by fluorescence in situ hybridization. In addition, androgen receptor gene somatic mutations were detected by next-generation sequencing. However, 6 months postoperatively, the patient had neither developed a recurrence nor received adjuvant radiotherapy and chemotherapy. Accurate diagnosis depends on morphological and immunohistochemical examination and a proper molecular analysis, and novel technologies can detect a wide variety of genetic alterations. Although androgen receptor somatic mutations cannot provide addition treatment at present, surgical resection with a clean margin and follow-up is an appropriate approach.

scholarly journals Clinical Scales Used in Motor Neuron Disease

2021 ◽  
Vol 39 (2 Suppl) ◽  
pp. 77-86
Author(s):  
Seong-il Oh ◽  
Jin-Sung Park ◽  
Jung-Joon Sung ◽  
Seung Hyun Kim
Keyword(s):  
Clinical Trials ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Motor Nerve ◽  
Clinical Manifestations ◽  
Research Field ◽  
Clinical Progression ◽  
Clinical Scales ◽  
Different Types

Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.

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