Juvenile primary lateral sclerosis (JPLS) is a very rare motor neuron disease characterized by progressive upper motor neuron dysfunction leading to loss of ability to walk with wheelchair dependence, and subsequently, loss of motor speech production.
The prevalence and incidence of JPLS are not known. A very small number of cases, around 4 patients, have been reported to date with this condition. The disorder has been described in various ethnic groups.
Affected patients are usually normal at birth and have normal early development. During the second year of life, they lose the ability to walk (some patients never walk due to early severe spasticity) and then develop slowly progressive upper motor neuron disorders including pseudobulbar palsy and spastic quadriplegia. Other signs include clumsiness, muscle weakness and balance difficulties. Patients generally become wheelchair dependent by adolescence. Between 2 and 10 years of age, motor speech production is lost causing dysarthria, dysphagia and drooling. Cognitive function is generally not affected.
Mutations in the ALS2 gene (2q33-q35) encoding alsin, a protein that is abundant in motor neurons, and less commonly mutations in the ERLIN2 gene (8p11.2) have been reported.
Diagnosis is based on the characteristic clinical signs and can be confirmed by molecular genetic testing. Electromyography, nerve conduction velocities, visual evoked potentials, and brain stem auditory evoked potentials are all normal, while transcranial magnetic stimulation shows no motor evoked potentials. Computed tomography (CT) and magnetic resonance imaging (MRI) scans of the brain and spinal cord are normal.
Differential diagnoses include the allelic disorders juvenile amyotrophic lateral sclerosis and infantile-onset ascending hereditary spastic paralysis (see these terms).
Prenatal diagnosis for at-risk pregnancies is possible if the disease-causing mutations have been identified in the family.
JPLS is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes and are therefore asymptomatic carriers. Genetic counseling should be provided to affected families.
Management primarily involves physical and occupational therapy to promote mobility and independence.
The prognosis is guarded, with the clinical signs having a major impact on quality of life.
Last update: February 2014