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juvenile primary lateral sclerosis (JPLS) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

juvenile primary lateral sclerosis

MONDO:0011663

Also known as:JPLSjuvenile PLSPLS juvenile

Overview

Juvenile primary lateral sclerosis (JPLS) is a very rare motor neuron disease characterized by progressive upper motor neuron dysfunction leading to loss of the ability to walk with wheelchair dependence, and subsequently, loss of motor speech production.

GeneticsAutosomal recessive · ALS2 (chr 2)

ResearchLimited published research (5 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Babinski sign, Spastic tetraparesis, Appendicular spasticity, and Pseudobulbar paralysis and others; and common findings: Decreased compound muscle action potential amplitude and Loss of ambulation. 19 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	11	Difficulty swallowing (dysphagia), Babinski sign, Spastic dysarthria

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

ALS2 encodes alsin Rho guanine nucleotide exchange factor ALS2 (1,657 aa). May act as a GTPase regulator. Controls survival and growth of spinal motoneurons Highest expression in Brain Cerebellar Hemisphere (126.8 TPM) and Brain Cerebellum (115.6 TPM).

Juvenile primary lateral sclerosis is associated with mutations in the ALS2 gene on chromosome 2.

The ALS2 protein participates in RAB5 GEFs exchange GTP for GDP on RAB5, RAC1 GEFs activate RAC1, and RHOA GEFs activate RHOA pathways.

ALS2 is classified as a druggable target with score 0.0.

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for ALS2-related disorder have been published. ALS2-related disorder comprises a phenotypic continuum of three phenotypes previously thought to be distinct entities: infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS). Suggestive Findings ALS2-related disorder should be suspected in individuals with the following clinical, electrophysiologic, and neuroimaging findings and family history. Clinical Findings • Childhood onset of progressive upper motor neuron involvement (spasticity affecting the legs and upper limbs) • Variably lower motor neuron involvement (muscle atrophy and sensory disturbances) • Later pseudobulbar involvement including speech • Preservation of cognitive function Electrophysiologic Findings shows the results of various electrophysiologic studies in the different phenotypes of ALS2-related disorders. Note that nerve conduction velocities, visual evoked potentials, and brain stem auditory evoked potentials are normal in all phenotypes. Table 1. Electrophysiologic Studies in ALS2-Related Disorder by Phenotype Study | Phenotype

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for juvenile primary lateral sclerosis. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines specifically for ALS2-related disorder have been published. Management is similar to that of persons with the wider range of amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), and other neurodegenerative conditions. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ALS2-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with ALS2-related Disorder

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with ALS2-related Disorder

System/Concern | Evaluation | Frequency

Neurologic

involvement | Neurologic exam to monitor progression of existing findings development of new findings | Annually or as needed

Development /

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for juvenile primary lateral sclerosis.

13 publications have been identified in PubMed for juvenile primary lateral sclerosis. Kisho has analyzed 5 by research type. Research spans Basic Science / Preclinical (60%), Diagnostic / Biomarker (20%), and Review / Meta-Analysis (20%).

Recent Publications

Sanhueza-Novoa P (2026). [PMID: 40664050](https://pubmed.ncbi.nlm.nih.gov/40664050/). *Spectrochim Acta A Mol Biomol Spectrosc*. [Diagnostic / Biomarker]
Dziadkowiak E (2025). [PMID: 41517538](https://pubmed.ncbi.nlm.nih.gov/41517538/). *J Clin Med*. [Review / Meta-Analysis]
Yoganathan S (2025). [PMID: 39424348](https://pubmed.ncbi.nlm.nih.gov/39424348/). *Neuropediatrics*. [Basic Science / Preclinical]
Laverde-Paz MJ (2025). [PMID: 40957373](https://pubmed.ncbi.nlm.nih.gov/40957373/). *Stem Cell Res*. [Basic Science / Preclinical]
Lavajoo Bolgouri F (2024). [PMID: 39518814](https://pubmed.ncbi.nlm.nih.gov/39518814/). *Animals (Basel)*. [Basic Science / Preclinical]

Data assembled from 7 of 12 sources · Last updated Sep 19, 2026, 3:55 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:606353

Orphanet

European rare disease database

Orphanet:247604

GARD

Genetic and Rare Diseases Info Center

GARD:4485

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

IAHSP	JPLS	JALS
MEP	Severe dysfunction of the corticospinal tracts1	NA
SSEP	Normal in early stages; abnormal in later stages	Poorly configured; normal central conduction
EMG	No signs of denervation	No signs of denervation

System/Concern	Evaluation	Comment
Neurologic	By an experienced neurologist	For evidence of UMN, LMN, cranial nerve involvement Developmental assessment
dislocation	By experienced orthopedist	Musculoskeletal/
ADL	Physical medicine rehab / PT/OT eval	To incl assessment of:; Gross motor fine motor skills; Mobility, ADL, need for adaptive devices; Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)
Dysarthria	By speech language therapist	Consider need for alternative communication.
Dysphagia	Gastroenterology / nutrition / feeding team eval	To incl eval of aspiration risk nutritional status; Consider eval for gastric tube placement in those w/dysphagia /or aspiration risk. Oculomotor
involvement	Ophthalmologic exam	Incl assessment of ocular movements Bladder
dysfunction	Urologist	Assess for bladder spasticity w/frequency urgency of micturition. Bowel
dysfunction	Gastroenterologist	Assess for signs symptoms related to immobility. Genetic
counseling	By genetics professionals1	To inform affected persons their families re nature, MOI, implications of ALS2-related disorder to facilitate medical personal decision making Family support/ resources
Treatment of Manifestations in Individuals with ALS2-related Disorder Manifestation/Concern	Treatment	Considerations/Other UMN involvement (spasticity) / LMN involvement
(weakness)	Orthopedics / physical medicine rehab / PT/OT	Stretching to help avoid contractures fractures; Consider need for orthotics, positioning mobility devices (e.g., motorized chairs), disability parking placard. Developmental/
educational issues	See .	—
Scoliosis/hip dislocation	Per treating orthopedist	—
Musculoskeletal/ADL	PT OT to promote mobility independence	—
Dysarthria	Speech language therapy	Use of computer technologies devices adapted to facilitate writing voice communication
Dysphagia	Gastrostomy tube placement may be required for persistent feeding issues.	Dietary supplements as needed to maintain weight
Bladder dysfunction	Antispasticity medications, catheter	Per routine management of spastic bladder
Bowel dysfunction	Monitor for constipation.	Stool softeners, prokinetics, osmotic agents, or laxatives as needed Family support/ resources

Kisho

juvenile primary lateral sclerosis

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Hereditary Spastic Paraplegia (HSP)

Therapies Under Investigation

Clinical Trials

Spine and hips

Dysarthria

Dysphagia

Latest News & Developments

Early Cognitive and Behavioral Changes in Primary Lateral Sclerosis: A Population-Based Study.

Primary Lateral Sclerosis French National Diagnostic and Care Protocol.

juvenile primary lateral sclerosis

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Hereditary Spastic Paraplegia (HSP)

Therapies Under Investigation

Clinical Trials

Spine and hips

Dysarthria

Dysphagia

Latest News & Developments

Early Cognitive and Behavioral Changes in Primary Lateral Sclerosis: A Population-Based Study.

Primary Lateral Sclerosis French National Diagnostic and Care Protocol.