Amyotrophic Lateral Sclerosis (ALS), also referred to as Lou Gehrig’s or Charcot’s disease, is one of the most common adult-onset neuromuscular disorders worldwide. ALS is a rapidly progressive and fatal neurodegenerative disease affecting all ethnicities with an annual incidence ~1 to 2 per 100,000 and an estimated prevalence from 2-8 per 100,000.¹ The mean age at onset is 60 years old with death usually resulting within 1-5 years of onset due to respiratory failure.² There is a slight male preference (M: F ratio~1.5:1), however studies now suggest that as the incidence age increases both sexes are equally affected.^3,4 Roughly 90% of ALS patients have no family history of ALS and are referred to as having sporadic ALS (SALS). The remaining 10% of ALS cases are referred to as familial ALS (FALS) in which individuals have at least one affected family member.⁵ FALS is divided into eleven different types of ALS (ALS1-11) and all types, with the exception of ALS2 and ALS5, are inherited in an autosomal dominant manner with high penetrance.³ 

Of the eleven FALS types, five types of autosomal dominant ALS (AD-ALS) have been associated with mutations in single genes. These five genes are: SOD1 (ALS1), TARDBP (ALS10), ANG (ALS9), FUS (ALS6), and FIG4 (ALS11). Twenty percent (20%) of FALS cases have identified mutations in the SOD1 gene⁵, ~5% have identified mutations in the TARDBP gene^3,6, with mutations in FUS, ANG, and FIG4 representing a combined 5%.^2,7,8 

ALS is characterized by the degeneration and death of both the upper and lower motor neurons in the cerebral cortex, brainstem, and spinal cord.^2,3 Some of the hallmarks of the disease include progressive muscle weakness, muscle atrophy, and fasciculations. Initial symptoms are dependent on whether the patient presents the limb (classic) or bulbar onset form.¹ Approximately two thirds of patients will present symptoms of the limb form which includes asymmetric focal muscle weakness, muscle twitches or cramps, or fasciculations. Patients presenting bulbar ALS symptoms usually manifest with dysarthria or dysphagia. As the disease progresses, patients will develop both limb and bulbar symptoms along with increasing issues ultimately leading to paralysis. Prognosis for ALS patients is poor with an average survival time of 2-3 years for the bulbar form and 3-5 years for the limb form upon the onset of symptoms.³