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Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Juvenile primary lateral sclerosis

Reviewed July 2013

What is juvenile primary lateral sclerosis?

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.

How common is juvenile primary lateral sclerosis?

Juvenile primary lateral sclerosis is a rare disorder, with few reported cases.

What genes are related to juvenile primary lateral sclerosis?

Mutations in the ALS2 gene cause most cases of juvenile primary lateral sclerosis. This gene provides instructions for making a protein called alsin. Alsin is abundant in motor neurons, but its function is not fully understood. Mutations in the ALS2 gene alter the instructions for producing alsin. As a result, alsin is unstable and is quickly broken down, or it cannot function properly. It is unclear how the loss of functional alsin protein damages motor neurons and causes juvenile primary lateral sclerosis.

Related Gene(s)

Changes in these genes are associated with juvenile primary lateral sclerosis.

  • ALS2
  • ERLIN2

How do people inherit juvenile primary lateral sclerosis?

When caused by mutations in the ALS2 gene, juvenile primary lateral sclerosis is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of juvenile primary lateral sclerosis?

These resources address the diagnosis or management of juvenile primary lateral sclerosis and may include treatment providers.

  • Gene Review: ALS2-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1243)
  • Genetic Testing Registry: Juvenile primary lateral sclerosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853396)

You might also find information on the diagnosis or management of juvenile primary lateral sclerosis in Educational resources and Patient support.

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about juvenile primary lateral sclerosis?

You may find the following resources about juvenile primary lateral sclerosis helpful. These materials are written for the general public.

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

What other names do people use for juvenile primary lateral sclerosis?

  • JPLS
  • juvenile PLS
  • PLSJ
  • primary lateral sclerosis, juvenile

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about juvenile primary lateral sclerosis?

Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding juvenile primary lateral sclerosis?

autosomal ; autosomal recessive ; cell ; difficulty swallowing ; gene ; inherited ; juvenile ; motor ; protein ; recessive ; sclerosis ; spasticity

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

References

  • Gene Review: ALS2-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1243)
  • Hadano S, Kunita R, Otomo A, Suzuki-Utsunomiya K, Ikeda JE. Molecular and cellular function of ALS2/alsin: implication of membrane dynamics in neuronal development and degeneration. Neurochem Int. 2007 Jul-Sep;51(2-4):74-84. Epub 2007 May 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17566607?dopt=Abstract)
  • Mintchev N, Zamba-Papanicolaou E, Kleopa KA, Christodoulou K. A novel ALS2 splice-site mutation in a Cypriot juvenile-onset primary lateral sclerosis family. Neurology. 2009 Jan 6;72(1):28-32. doi: 10.1212/01.wnl.0000338530.77394.60. (http://www.ncbi.nlm.nih.gov/pubmed/19122027?dopt=Abstract)
  • Panzeri C, De Palma C, Martinuzzi A, Daga A, De Polo G, Bresolin N, Miller CC, Tudor EL, Clementi E, Bassi MT. The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain. 2006 Jul;129(Pt 7):1710-9. Epub 2006 May 2. (http://www.ncbi.nlm.nih.gov/pubmed/16670179?dopt=Abstract)
  • Yang Y, Hentati A, Deng HX, Dabbagh O, Sasaki T, Hirano M, Hung WY, Ouahchi K, Yan J, Azim AC, Cole N, Gascon G, Yagmour A, Ben-Hamida M, Pericak-Vance M, Hentati F, Siddique T. The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet. 2001 Oct;29(2):160-5. (http://www.ncbi.nlm.nih.gov/pubmed/11586297?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2013
Published: July 27, 2015