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Publications about genetic testing for neurological disorders
  1. NGS Panel – Genetic Testing for Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS)

May 11, 2018

Disease summary:

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of the upper and lower motor neurons. Most cases appear to be sporadic, but 5-10% of cases have a family history of the disease (FALS) 1. To date, more than a dozen causative genes have been identified in hereditary ALS and more than 30 potential causative or disease-modifying genes have also been identified 2, 3


Autosomal dominant, autosomal recessive, X-linked dominant

Prevalence: 4-8/100,000 1, 4

Major clinical symptoms 1, 5:

  • Asymmetric focal weakness of the extremities (stumbling or poor handgrip)
  • Dysarthria
  • Dysphagia)
  • Muscle fasciculations
  • Muscle cramps

Presence of all of the following clinical features 1, 5:

  • Signs of lower motor neuron (LMN) degeneration by clinical, electrophysiologic, or neuropathologic examination
  • Signs of upper motor neuron (UMN) degeneration by clinical examination
  • Progressive spread of symptoms or signs within a region or to other regions
  • Absence of evidence of other diseases that could cause UMN or LMN degeneration and/or explain the electrophysiologic or neuropathologic results

For familial cases of ALS: Identification of a heterozygous pathogenic variant in one of the following genes 2, 3 (Table 1):

  • SOD1 (frequency of pathogenic variants approximately 20%) 1-3
  • C9orf72 (23%-30%) 1-3
  • TARDBP (1%-4%) 1-3
  • FUS (4%) 1-3
  • SETX, FIG4, ANG and others (Table 1).

There is no cure for ALS to date, but symptomatic treatment can relieve symptoms 1, 6.

  • Care by a multidisciplinary team (neurologist, pulmonologist, speech, physical and occupational therapist, nutritionist, psychologist, social worker, and genetics professional) 6.
  • The two FDA–approved drugs riluzole and edaravone, slow the progression of symptoms
  • Antidepressants, bensodiazepines, baclofen, for muscle cramps and spasticity
  • Ventilator assistance
  • Spinal and bulbar muscular atrophy
  • Spinal muscular atrophy
  • Distal hereditary motor neuronopathy type VIIB
  • Primary lateral sclerosis
  • Hereditary spastic paraplegia
  • Hexosaminadase A deficiency
  • Inclusion body myopathy associated with Paget disease of bone and/or frontotemporal dementia 

 

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for ALS using NGS Panel Genomic:

Step 1: Whole genome sequencing from a single filter card (drop of blood), covering the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the ALS panel. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no pathogenic variant is identified in Step1, continue with bioinformatics analysis covering genes that are either implicated or associated with overlapping phenotype or similar pathways.   

  • Individuals with a positive family history of ALS
  • Individuals with most common symptoms of ALS (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of ALS can allow for genetic counseling and may direct medical management.