The phenotypic variability of amyotrophic lateral sclerosis

  title={The phenotypic variability of amyotrophic lateral sclerosis},
  author={Bart Swinnen and Wim Robberecht},
  journal={Nature Reviews Neurology},
Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3–5 years after onset—a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. Here, we review the phenotypic variability of ALS and how… 

Amyotrophic lateral sclerosis mimics

Understanding the spectrum of clinical presentations of ALS and its mimics is paramount, and the clinician must correctly identify these disorders to avoid the misdiagnosis ofALS and to initiate effective treatment where available.

Genotypic and Phenotypic Heterogeneity in Amyotrophic Lateral Sclerosis

The major genes implicated in the pathogenesis of motor neuron diseases; the clinical, pathological, and genetic links between ALS and frontotemporal dementia; and the vast genotypic and phenotypic heterogeneity of ALS are discussed.

New ALS‐Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis

Considering the increasing number of spectra of ALS, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases.

Phenotypic variability and its pathological basis in amyotrophic lateral sclerosis

Underlying region‐specific cellular vulnerability may exist in the upper and lower motor neurons and frontotemporal system in patients with ALS, and this vulnerability may be linked to the macroscopic propensities of the sites of onset, and may also determine the direction and rate of progression of the lesions.

Amyotrophic lateral sclerosis – aetiology, diagnostics and multidirectional, team, long-term care

Doping is still based on a correlation of interview and clinical picture with the results of diagnostic imaging, electrophysiological examinations and some serological tests, however, more and more often the role of genotype interaction with environmental factors is suggested.

Diagnosis and Clinical Management of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders

Although ALS cannot be cured, implementation of appropriate symptomatic treatment is valuable and recognition of suspicious symptoms and the appropriate laboratory evaluation are essential to limit diagnostic delay and avoid unnecessary testing and procedures.

Atypical Familial Amyotrophic Lateral Sclerosis with Slowly Progressing Lower Extremities-predominant Late-onset Muscular Weakness and Atrophy

A new atypical fALS family with a benign clinical course is reported and two candidate gene mutations of PLEC and ST3GAL6 linked to this phenotype are identified.



Clinical and genetic heterogeneity of amyotrophic lateral sclerosis

Although clinical picture of amyotrophic lateral sclerosis (ALS) is a stereotypical one, resulting from combination of signs secondary to dysfunction of both upper motor neuron (UMN) and lower motor

The Frontotemporal Syndromes of ALS. Clinicopathological Correlates

The contemporary clinical, genetic and neuropathological characteristics of the frontotemporal syndromes of ALS are reviewed and it is proposed that as opposed to being a FTLD in which TDP-43 is the primary disease protein (FTLD-TDP), they represent a hybrid of both T DP-43 and tau pathology.

Autonomic impairment in amyotrophic lateral sclerosis

The wide range of autonomic involvement, together with results suggesting cognitive and extrapyramidal dysfunction, supports the view that ALS is a multisystem degenerative disease.

State of play in amyotrophic lateral sclerosis genetics

Current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72 and PFN1 are summarized and how each new genetic discovery is broadening the phenotype associated with the clinical entity the authors know as ALS is outlined.

ALS motor phenotype heterogeneity, focality, and spread

Heterogeneity of motor phenotypes suggests motor neuron degeneration in ALS is in actuality a very orderly and actively propagating process and that fundamental molecular mechanisms may be uniform and their chief properties deduced.

The epidemiology of ALS: a conspiracy of genes, environment and time

The relationship between genetic and environmental risk factors is examined, and a disease model in which ALS is considered to be the result of environmental risks and time acting on a pre-existing genetic load is proposed, followed by an automatic, self-perpetuating decline to death.

Cognitive impairment in amyotrophic lateral sclerosis

The changing scene of amyotrophic lateral sclerosis

New findings in ALS research are summarized, what they have taught us about this disease are discussed and issues that are still outstanding are examined.

Novel FUS deletion in a patient with juvenile amyotrophic lateral sclerosis.

This work sequenced the coding exons of SOD1, TARDBP, and FUS in a 19-year-old patient experiencing rapid degeneration of upper and lower motor neurons and confirmed that FUS mutations can lead to an early-onset malignant form of ALS.

Clinical genetics of amyotrophic lateral sclerosis: what do we really know?

The only clinical feature that distinguishes recognized hereditary from apparently sporadic ALS is a lower mean age of onset in the former, and all the clinical features reported in hereditary cases have also been observed in sporadic cases.