Amyotrophic Lateral Sclerosis (ALS)
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.
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.