Encyclopedia
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.
- genetic conditions
1. Introduction
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.
2. Frequency
Juvenile primary lateral sclerosis is a rare disorder, with few reported cases.
3. Causes
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.
4. Inheritance
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.
5. Other Names for This Condition
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JPLS
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juvenile PLS
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PLSJ
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primary lateral sclerosis, juvenile
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/juvenile-primary-lateral-sclerosis
References
- Hadano S, Kunita R, Otomo A, Suzuki-Utsunomiya K, Ikeda JE. Molecular andcellular function of ALS2/alsin: implication of membrane dynamics in neuronaldevelopment and degeneration. Neurochem Int. 2007 Jul-Sep;51(2-4):74-84.
- Mintchev N, Zamba-Papanicolaou E, Kleopa KA, Christodoulou K. A novel ALS2splice-site mutation in a Cypriot juvenile-onset primary lateral sclerosisfamily. Neurology. 2009 Jan 6;72(1):28-32. doi:10.1212/01.wnl.0000338530.77394.60.
- Orrell RW. ALS2-Related Disorders. 2005 Oct 21 [updated 2016 Jan 28]. In: AdamMP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle;1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1243/
- 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(Pt7):1710-9.
- 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 threeguanine-nucleotide exchange factor domains, is mutated in a form of recessiveamyotrophic lateral sclerosis. Nat Genet. 2001 Oct;29(2):160-5.
