scholarly journals Upper Motor Neuron Disorders: Primary Lateral Sclerosis, Upper Motor Neuron Dominant Amyotrophic Lateral Sclerosis, and Hereditary Spastic Paraplegia

2021 ◽  
Vol 11 (5) ◽  
pp. 611
Author(s):  
Timothy Fullam ◽  
Jeffrey Statland
Keyword(s):  
Motor Neuron ◽  
Hereditary Spastic Paraplegia ◽  
Diagnostic Tests ◽  
Primary Lateral Sclerosis ◽  
Spastic Paraplegia ◽  
Disease Modifying ◽  
Primary Lateral ◽  
Early Phases ◽  
Lateral Sclerosis ◽  
Motor Neuron Syndrome

Following the exclusion of potentially reversible causes, the differential for those patients presenting with a predominant upper motor neuron syndrome includes primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), or upper motor neuron dominant ALS (UMNdALS). Differentiation of these disorders in the early phases of disease remains challenging. While no single clinical or diagnostic tests is specific, there are several developing biomarkers and neuroimaging technologies which may help distinguish PLS from HSP and UMNdALS. Recent consensus diagnostic criteria and use of evolving technologies will allow more precise delineation of PLS from other upper motor neuron disorders and aid in the targeting of potentially disease-modifying therapeutics.

Upper Motor Neuron Disorders Hereditary Spastic Paraplegia and Primary Lateral Sclerosis

2017 ◽  
Author(s):  
Sabrina Paganoni ◽  
Nazem Atassi
Keyword(s):  
Motor Neuron ◽  
Hereditary Spastic Paraplegia ◽  
Disease Modeling ◽  
Primary Lateral Sclerosis ◽  
Spastic Paraplegia ◽  
Underlying Pathophysiology ◽  
Primary Lateral ◽  
Lateral Sclerosis

Upper motor neuron (UMN) syndromes are a group of rare, degenerative neurological disorders that are classified as either hereditary spastic paraplegia (HSP) or primary lateral sclerosis (PLS). Our understanding of their underlying pathophysiology is unfortunately very limited and has been a significant barrier to the development of disease-modifying treatments. Recent advances in genetics and in vitro and in vivo disease modeling have provided new insights into disease mechanisms and hold the promise to lead to the future development of mechanism-based therapies.

scholarly journals Alsin Related Disorders: Literature Review and Case Study with Novel Mutations

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Filipa Flor-de-Lima ◽  
Mafalda Sampaio ◽  
Nahid Nahavandi ◽  
Susana Fernandes ◽  
Miguel Leão
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Hereditary Spastic Paraplegia ◽  
Gene Mutations ◽  
Heterozygous Mutation ◽  
Sequencing Analysis ◽  
Primary Lateral Sclerosis ◽  
Spastic Paraplegia ◽  
Juvenile Amyotrophic Lateral Sclerosis ◽  
Primary Lateral ◽  
Lateral Sclerosis

Mutations in theALS2gene cause three distinct disorders: infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and autosomal recessive juvenile amyotrophic lateral sclerosis. We present a review of the literature and the case of a 16-year-old boy who is, to the best of our knowledge, the first Portuguese case with infantile ascending hereditary spastic paraplegia. Clinical investigations included sequencing analysis of the ALS2 gene, which revealed a heterozygous mutation in exon 5 (c.1425_1428del p.G477Afs*19) and a heterozygous and previously unreported variant in exon 3 (c.145G>A p.G49R). We also examined 42 reported cases on the clinical characteristics and neurophysiological and imaging studies of patients with known ALS2 gene mutations sourced from PubMed. This showed that an overlap of phenotypic manifestations can exist in patients with infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and juvenile amyotrophic lateral sclerosis.

Exome Sequencing Identifies a Mutation (Y740C) in Spastic Paraplegia 7 Gene Associated with Adult-Onset Primary Lateral Sclerosis in a Chinese Family

2019 ◽  
Vol 81 (1-2) ◽  
pp. 87-93 ◽  
Author(s):  
Yihui Liu ◽  
Jiang Xu ◽  
Wanyun Tao ◽  
Changbiao Fu ◽  
Jiangbing Liu ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Exome Sequencing ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Primary Lateral Sclerosis ◽  
Adult Onset ◽  
Spastic Paraplegia ◽  
Limb Weakness ◽  
Primary Lateral ◽  
Lateral Sclerosis

Background: Primary lateral sclerosis (PLS) is considered a rare variant of motor neuron disease (MND) characterized by selective upper motor neuron dysfunction leading to limb weakness, spasticity, and even bulbar symptoms. Previous studies have demonstrated that mutations in ALSIN, spastic paraplegia 7 (SPG7), TBK1, ALS2, ERLIN2, and FIG4 are responsible for PLS. Most of them occurred in childhood to young-adult onset patients. The aim of this study was to identify the genetic lesion of patients with adult-onset PLS. Methods: We applied whole-exome sequencing (WES) and MND and ataxia-related genes filtering strategies to discover the genetic factors in a Chinese adult-onset PLS family. Sanger sequencing was used in the cosegregation analysis in the affected family members. Results: A mutation (c.2219A>G/p.Y740C) in exon 17 of SPG7 was identified in an adult-onset PLS patient and cosegregated with the affected members in this family. Meanwhile, the mutation was predicted to be deleterious by 3 bioinformatics programs (Polymorphism phenotyping-2, sorting intolerant from tolerant and MutationTaster). This variant may cause the structure changes of paraplegin protein. Conclusions: We employed WES to detect a missense mutation of SPG7 gene in a PLS family. This finding expands the spectrum of known SPG7 mutations, and it may contribute to novel approaches to genetic diagnosis and counseling of families with PLS.

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