Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a progressive disease that affects the control of muscle movement by damaging specialized nerve cells (motor neurons) in the spinal cord and the part of the brain that is connected to the spinal cord (brain stem). Most cases of amyotrophic lateral sclerosis are sporadic, which means there is no previous family history of this disorder, and the cause may not be genetic. The different types of inherited amyotrophic lateral sclerosis are distinguished by genetic cause, pattern of inheritance, age when symptoms begin, and how quickly the disease progresses.

Genetic changes are related to the following types of amyotrophic lateral sclerosis.

• amyotrophic lateral sclerosis, type 1
• amyotrophic lateral sclerosis, type 2
• amyotrophic lateral sclerosis, type 4

Additional types of amyotrophic lateral sclerosis have been reported, but the responsible mutations have not been adequately described.

The first signs of amyotrophic lateral sclerosis may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Speech may become slurred, and later there is difficulty chewing or swallowing. The muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue wastes away (atrophies). Individuals with this disorder lose their strength and the ability to walk and use their hands and arms. In late stages of the disease, breathing becomes difficult because the muscles of the respiratory system weaken. Most people with amyotrophic lateral sclerosis die from respiratory failure, usually from 3 to 15 years after the onset of symptoms.

An estimated 5,000 people in the United States are diagnosed with amyotrophic lateral sclerosis each year. Worldwide, this disorder occurs in 4 to 8 per 100,000 individuals.

Mutations in the ALS2, KIAA0625, and SOD1 genes cause amyotrophic lateral sclerosis.

Variations of the NEFH gene increase the risk of developing amyotrophic lateral sclerosis.

More than 90 percent of amyotrophic lateral sclerosis cases are classified as sporadic, and the cause of these cases remains largely unknown. Inherited types of amyotrophic lateral sclerosis (5-10 percent of all cases) can be caused by mutations in the SOD1, ALS2, or KIAA0625 (also called SETX) gene. These mutations contribute to the decline and death of motor neurons, which leads to muscle weakness and atrophy. Not all inherited cases, however, are due to SOD1, ALS2, or KIAA0625 mutations. Other genetic causes are involved, but they have not been identified or fully characterized. Additionally, mutations in the NEFH gene appear to increase the risk of developing amyotrophic lateral sclerosis.

The pattern of inheritance varies with the type of amyotrophic lateral sclerosis. Please refer to a specific type of amyotrophic lateral sclerosis for an explanation of inheritance.

You may find the following resources about amyotrophic lateral sclerosis helpful.

• NIH Publications - National Institutes of Health
  National Institute for Neurological Disorders and Stroke
• MedlinePlus - Health Information (2 links)
• Genes and Disease - Genetic disorder summaries
• Educational resources - Information pages (4 links)
• Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog (3 links)

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What are the different ways in which a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

atrophy ; brain stem ; familial ; family history ; gene ; motor neuron ; mutation ; nerve cell ; neuron ; pattern of inheritance ; respiratory ; sclerosis ; sign ; sporadic ; symptom

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.