Genetic Forms of ALS  

ALS can be grouped in multiple ways. Most known are two classifications based on the underlying cause of the disease, either familial or sporadic. Sometimes ALS is also classified by the clinical onset or progression of the disease. This is called the disease phenotype or the observable characteristics of the disease.  

Familial ALS

About 10 percent of cases are classified as hereditary or Familial ALS (fALS). Although clinically indistinguishable from Sporadic ALS, Familial ALS or fALS is inherited through an autosomal dominant gene mutation. When we are born, we get one copy of DNA from each parent, but normally only one of these genes expresses itself. The expressed gene is considered the more dominant gene. An autosomal dominant gene is a gene that will always be expressed in a carrying individual. There are several different genes that have been associated with fALS. The first discovered gene is SOD1 (superoxide dismutase 1), which makes up 12 percent of fALS cases. Because there are so many different genes, most cases are not tested for fALS unless there is a known history of the disease in the patient's family. 

Sporadic ALS 

Sporadic ALS (sALS) makes up the other 90 percent of ALS cases in the U.S. Men are one and a half times more likely to be diagnosed with sALS than women. The cause of sALS is not well understood, but research has connected it with various sources. Around 10 percent of sALS cases have a known genetic mutation. Other correlations are found in environmental factors, such as active-duty involvement in U.S. military service and smoking. Other factors such as stress, poor sleep, trauma, and strenuous physical exertion may also be involved in the development of sALS. 

Clinical Phenotypes of ALS 

Clinical phenotypes are based on the different observable disease onset locations. ALS diagnosis can vary depending on which parts of the body the disease onset begins. Regardless of when disease onset begins, the disease will eventually spread to the rest of the body.  

Limb-onset ALS  

Limb onset ALS often begins in the hands or arms. People often have trouble with everyday activities such as buttoning a shirt, writing or turning a key. About 70% of ALS patients are diagnosed with Limb-onset ALS. Symptoms can also initiate in the legs, making it difficult to walk or run without tripping or stumbling. Symptoms then spread to the rest of the body.  

Bulbar-onset ALS 

Bulbar onset often first presents itself through speech or swallowing problems. About 25% of ALS patients are diagnosed with Bulbar-onset ALS. The disease then progresses to affect the limbs and other parts of the body.  

Similar Motor Neuron Diseases 

There are a handful of diseases that are similar to ALS but differ such that they have their own disease classification. There is some controversy as to whether these are actualy different motor neuron diseas or actual subsets of ALS.

Primary Lateral Sclerosis (PLS) 

PLS is similar to ALS in that motor neuron disease that causes neurons within the brain to break down slowly. The biggest difference is that it progresses more slowly than ALS and it is not fatal in most cases.  

Progressive Muscular Atrophy (PMA) 

PMA is similar to ALS in that it is classified by the slow breakdown of neurons. The difference is that it affects the lower motor neurons, as opposed to ALS which is classified by lower and upper neuron decay. Lower neurons are neurons that go from the spinal cord to the muscles where upper motor neurons are Nerve cells in the brain.  

ALS-plus Syndrome 

This diagnosis is described by additional symptoms beyond the typical ALS motor neuron decay. It Includes dementia, sensory loss, and other dysfunctions. One of any of these additional symptoms alongside traditional ALS is considered ALS-plus syndrome. 



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