Sporadic ALS
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About 90% of cases of amyotrophic lateral sclerosis (ALS), the progressive neurological disorder also known as Lou Gehrig’s disease, are characterized as sporadic ALS, meaning they occur spontaneously. The term sporadic in ALS means without a clear pattern, and the individuals with these cases have no known family history of the disease.
When more than one person in the same biological family has ALS, patients are said to have familial ALS. In both instances, ALS is marked by the loss of motor neurons, the specialized nerve cells that control movement.
The causes of sporadic ALS are not understood well, though a number of risk factors have been identified. It is thought that a complex interaction between genetics and environmental factors leads to the development of the disease.
Genetics and sporadic ALS
By definition, sporadic ALS affects only one person in a given biological family. As such, sporadic ALS is not hereditary — that is, the disease is not inherited via genes that are passed from parents to their biological children. Nonetheless, genetics are believed to play a substantial role in influencing a person’s risk of developing sporadic ALS.
In about 10% of sporadic ALS cases, patients carry a specific disease-associated mutation. The most commonly mutated genes in sporadic ALS are C9ORF72 and SOD1. C9ORF72 mutations are found in about 7% to 10% of cases, while SOD1 mutations are seen in about 1% to 2% of cases. These genes also are often mutated in familial ALS, though a number of other rarer mutations have also been identified in sporadic cases.
In some cases, these mutations may occur de novo, meaning that they appear for the first time in the affected individual. Generally speaking, this would be because the mutation developed in the individual sperm or egg cell prior to conception.
In most people with sporadic ALS, a specific disease-associated mutation is not identified. Genetics are still believed to influence disease risk in these cases, but the associations are thought to be more complex, with many different genetic variations interacting with each other and with environmental and lifestyle factors to determine disease risk.
Genetic testing for sporadic ALS
Because about 90% of people with sporadic ALS do not have a known disease-linked mutation, genetic testing will not provide actionable data for most patients with this ALS type.
However, in the rare cases where a mutation is found, this may provide useful information about the potential disease course and the risk of passing the mutation on to future generations. There also are experimental therapies being developed to target some specific mutations, so genetic testing may provide information about clinical trial eligibility for some patients.
The ALS Identified program, sponsored by Biogen and run by the diagnostic company Invitae, offers free genetic testing to people in the U.S. and Puerto Rico who have been diagnosed with ALS. The program includes tests for more than 20 ALS-linked genes. It also offers optional testing for genes that have shown a link to ALS but are not yet definitively proven to be associated with the disease.
Sporadic vs. familial
About 10% of ALS cases occur in people who have a family history of the disease; these cases are referred to as familial ALS. Any case where there is no family history is classified as sporadic ALS, also sometimes called a simplex case.
While disease-causing mutations are identified in patients with both disease types, familial ALS seems to have a greater genetic contribution, with approximately 60% of familial ALS cases having a known disease-associated mutation, as opposed to 10% of those with sporadic ALS.
However, even in cases where a disease-associated mutation is not found, genetics are still thought to play a role in influencing the disease. This is so in both the sporadic and familial types, though the specific associations are less well understood.
How ALS manifests among patients is widely variable, but the signs and symptoms of sporadic and familial ALS are believed to be generally comparable. Yet, those with sporadic ALS tend to experience their first symptoms somewhat later in life and also have more slowly progressive disease.
Sporadic ALS symptoms
Common symptoms of sporadic ALS include:
- muscle weakness, spasticity, and wasting
- trouble swallowing and speaking
- difficulty breathing
- constipation or other digestive issues
- cognitive problems and dementia
- pseudobulbar affect, characterized by uncontrolled bouts of laughing or crying
- mental health challenges.
ALS symptoms can begin at any age but usually appear in mid to late adulthood. The average age of onset for sporadic ALS is 58-63, while the disease typically starts at a mean age of 40-60 for those with familial ALS.
It is a progressive disease, meaning that patients tend to get worse and experience accumulating symptoms as time goes on. Disease symptoms usually start by affecting just one part of the body — most commonly a hand or foot, in people with limb-onset ALS, or less frequently muscles around the mouth, in bulbar-onset disease. These symptoms then gradually spread to affect the rest of the body.
There is no cure for sporadic ALS or any other form of the disease, but there are a number of treatments that can reduce symptoms and minimize disease complications.
Life expectancy is widely variable in people living with sporadic ALS. Most people survive about two to five years after their diagnosis, but it’s estimated that up to 20% of patients live longer than 10 years.
Sporadic ALS risk factors
Although the exact causes of sporadic ALS are not understood well, biological abnormalities such as irregular neuronal signaling, mitochondrial abnormalities, and inflammation have been implicated in the death and dysfunction of motor neurons that characterizes ALS.
These abnormalities may arise from inherent traits such as genetic variants, but also may be influenced by certain environmental factors and lifestyle habits. Potential risk factors for sporadic ALS include:
- male sex, with the disease being about 20% more common in men than in women
- age, with ALS most commonly developing between ages 55 and 75
- head injury and trauma
- exposure to toxic chemicals like pesticides and heavy metals
- certain viral infections, particularly with enteroviruses
- electric shocks or exposure to electromagnetic fields
- military service
- being very physically active.
ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about sporadic ALS
The main difference between sporadic and familial cases of amyotrophic lateral sclerosis (ALS) is whether or not there is a family history of the disease. When ALS affects more than one person in the same biological family, it’s referred to as familial ALS. The term sporadic ALS, on the other hand, is used to refer to any case of ALS in which there is no known family history of the disease. Sporadic ALS accounts for the vast majority — about 90% — of ALS cases.
Amyotrophic lateral sclerosis (ALS) is marked by the progressive damage and death of motor neurons, the specialized nerve cells responsible for controlling movement. In sporadic ALS, it’s not known exactly what causes the disease to develop, but a number of factors including genetics, environmental exposures, and lifestyle habits are all thought to affect a person’s risk.
Sporadic amyotrophic lateral sclerosis (ALS) can manifest at any age, but symptoms most commonly arise in middle or late adulthood. The average age at onset for sporadic ALS is 58-63. However, there have been reports of sporadic ALS cases manifesting during childhood and younger adulthood, with some cases being caused by de novo or specific new mutations in ALS-associated genes.
By definition, sporadic amyotrophic lateral sclerosis (ALS) affects only one person in a biological family. As such, sporadic ALS cannot be inherited, although patients may be born with certain genetic characteristics that contribute to their disease risk. When ALS affects multiple people in the same family, it is referred to as familial ALS.
There is no cure for any form of amyotrophic lateral sclerosis (ALS). However, there are available treatments that may slow ALS disease progression and extend survival. Therapies to help manage disease symptoms like spasticity and excessive drooling also are available.
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