ALS2 Gene

Infantile-onset ascending hereditary spastic paralysis is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and eventual paralysis of the lower limbs (paraplegia). The spasticity and paraplegia result from degeneration (atrophy) of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types involve additional areas of the nervous system, affecting the upper limbs and other areas of the body. Infantile-onset ascending hereditary spastic paralysis starts as a pure hereditary spastic paraplegia, with spasticity and weakness in the legs only, but as the disorder progresses, the muscles in the arms, neck, and head become involved and features of the disorder are more characteristic of the complicated type.

Affected infants are typically normal at birth, then within the first 2 years of life, the initial symptoms of infantile-onset ascending hereditary spastic paralysis appear. Early symptoms include exaggerated reflexes (hyperreflexia) and recurrent muscle spasms in the legs. As the condition progresses, affected children develop abnormal tightness and stiffness in the leg muscles and weakness in the legs and arms. Over time, muscle weakness and stiffness travels up (ascends) the body from the legs to the head and neck. Muscles in the head and neck usually weaken during adolescence; symptoms include slow eye movements and difficulty with speech and swallowing. Affected individuals may lose the ability to speak (anarthria). The leg and arm muscle weakness can become so severe as to lead to paralysis; as a result affected individuals require wheelchair assistance by late childhood or early adolescence. Intelligence is not affected in this condition.

A condition called juvenile primary lateral sclerosis shares many of the features of infantile-onset ascending hereditary spastic paralysis. Both conditions have the same genetic cause and significantly impair movement beginning in childhood; however, the pattern of nerve degeneration is different. Because of their similarities, these conditions are sometimes considered the same disorder.

Juvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and tightness (spasticity) of muscles in the arms, legs, and face. The features of this disorder are caused by damage to motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.

Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs, and difficulty with balance. As symptoms progress, the spasticity spreads to the arms and hands and individuals develop slurred speech, drooling, difficulty swallowing, and an inability to walk.

Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.

There are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.

The first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.

Approximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.

A rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms.

Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.

There are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.

The first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.

Approximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.

A rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms.