What are the other Names for this Condition? (Also known as/Synonyms)

• JALS (Juvenile Amyotrophic Lateral Sclerosis)
• Juvenile Amyotrophic Lateral Sclerosis (JALS)

What is Juvenile Primary Lateral Sclerosis? (Definition/Background Information)

• Juvenile Primary Lateral Sclerosis, or Juvenile Amyotrophic Lateral Sclerosis (JALS), is a rare motor neuron disease characterized by progressive degeneration of upper and lower motor neurons. Motor neurons are nerve cells that control voluntary muscle activity
• Symptoms of JALS typically begin before age 25, but often in early childhood. Symptoms include facial spasticity, dysarthria, and a spastic gait (manner of walking). Some people have uncontrolled laughter and weeping, mild wasting of the legs and hands, bladder dysfunction, and/or sensory disturbances
• The disease is usually slowly progressive but rate of progression varies. People with JALS may become unable to move by age 12 to age 50
• Juvenile Primary Lateral Sclerosis can be caused by mutations in any of several genes including ALS2, SIGMAR1, SPG11, SETX, SOD1, UBQLN2, FUS, and TARDBP. Mutations bay be inherited from a parent or may occur for the first time in a person with the disease. Inheritance may be autosomal recessive or autosomal dominant depending on the gene involved
• There is no specific treatment for Juvenile Primary Lateral Sclerosis. Management generally involves physical and occupational therapy to promote mobility and independence

(Source: Juvenile Primary Lateral Sclerosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Juvenile Primary Lateral Sclerosis? (Age and Sex Distribution)

• Juvenile Primary Lateral Sclerosis is a very rare congenital disorder. The presentation of symptoms often occurs in childhood, and generally before 25 years of age 
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors forJuvenile Primary Lateral Sclerosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Juvenile Primary Lateral Sclerosis can be inherited
• Children born to consanguineous parents may bear an increased risk of developing this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Juvenile Primary Lateral Sclerosis? (Etiology)

• Juvenile Primary Lateral Sclerosis may be caused by mutation(s) in several genes, including ALS2, SIGMAR1, SPG11, SETX, SOD1, UBQLN2, FUS, and TARDBP
• Depending on the specific causative gene mutation, the condition can either be inherited in an autosomal dominant or autosomal recessive manner
• Alternatively, some cases of Juvenile Primary Lateral Sclerosis may not be inherited, and develop sporadically due to “de-novo” mutation(s) in a gene known to cause the condition

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Juvenile Primary Lateral Sclerosis?

The signs and symptoms of Juvenile Primary Lateral Sclerosis may include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormal pyramidal signs
• Abnormal upper motor neuron morphology
• Amyotrophic lateral sclerosis
• Dysarthria
• EMG abnormality
• Gait disturbance
• Hyperreflexia
• Spasticity

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the bladder
• Decreased muscle mass
• Pseudobulbar behavioral symptoms
• Sensory neuropathy

(Source: Juvenile Primary Lateral Sclerosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

In addition, affected individuals may develop

• Excessive drooling
• Difficulty with swallowing (dysphagia)

How is Juvenile Primary Lateral Sclerosis Diagnosed?

Juvenile Primary Lateral Sclerosis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Differential diagnosis to rule out amyotrophic lateral sclerosis (ALS)
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Juvenile Primary Lateral Sclerosis?

The complications of Juvenile Primary Lateral Sclerosis may include:

• Speech impediment
• Weight loss due to difficulty with swallowing
• Urine retention and infections, due to abnormal bladder function
• Severely restricted mobility, with possible confinement to a wheelchair
• Reduced quality of life
• Depression

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Juvenile Primary Lateral Sclerosis Treated?

There is no cure for Juvenile Primary Lateral Sclerosis, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment measures may include:

• Physiotherapy to improve movement
• Occupational therapy

How can Juvenile Primary Lateral Sclerosis be Prevented?

Currently, Juvenile Primary Lateral Sclerosis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Juvenile Primary Lateral Sclerosis? (Outcomes/Resolutions)

• The prognosis of Juvenile Primary Lateral Sclerosis is guarded, since affected individuals may be unable to move of their own volition, and require wheelchair for mobility, severely affecting their quality of life 
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Juvenile Primary Lateral Sclerosis:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/