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Juvenile primary lateral sclerosis(PLSJ)

MedGen UID:
342870
Concept ID:
C1853396
Disease or Syndrome
Synonyms: PLS juvenile; PLSJ
SNOMED CT: Juvenile primary lateral sclerosis (717964007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ALS2 (2q33.1)
 
Monarch Initiative: MONDO:0011663
OMIM®: 606353
Orphanet: ORPHA247604

Disease characteristics

Excerpted from the GeneReview: ALS2-Related Disorder
ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts and comprises a clinical continuum of the following three phenotypes: Infantile ascending hereditary spastic paraplegia (IAHSP), characterized by onset of spasticity with increased reflexes and sustained clonus of the lower limbs within the first two years of life, progressive weakness and spasticity of the upper limbs by age seven to eight years, and wheelchair dependence in the second decade with progression toward severe spastic tetraparesis and a pseudobulbar syndrome caused by progressive cranial nerve involvement. Juvenile primary lateral sclerosis (JPLS), characterized by upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia without dementia or cerebellar, extrapyramidal, or sensory signs. Juvenile amyotrophic lateral sclerosis (JALS or ALS2), characterized by onset between ages three and 20 years. All affected individuals show a spastic pseudobulbar syndrome (spasticity of speech and swallowing) together with spastic paraplegia. Some individuals are bedridden by age 12 to 50 years. [from GeneReviews]
Authors:
Richard W Orrell   view full author information

Additional descriptions

From OMIM
Although primary lateral sclerosis is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria established (Pringle et al., 1992). PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons. A diagnosis of PLS is essentially one of exclusion (Sotaniemi and Myllyla, 1985; Younger et al., 1988; Yang et al., 2001).  http://www.omim.org/entry/606353
From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/juvenile-primary-lateral-sclerosis

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Pseudobulbar paralysis
MedGen UID:
10989
Concept ID:
C0033790
Disease or Syndrome
Bilateral impairment of the function of the cranial nerves 9-12, which control musculature involved in eating, swallowing, and speech. Pseudobulbar paralysis is characterized clinically by dysarthria, dysphonia, and dysphagia with bifacial paralysis, and may be accompanied by Pseudobulbar behavioral symptoms such as enforced crying and laughing.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
Spastic dysarthria
MedGen UID:
105312
Concept ID:
C0454596
Finding
A type of dysarthria related to bilateral damage of the upper motor neuron tracts of the pyramidal and extra- pyramidal tracts. Speech of affected individuals is slow, effortful, and has a harsh vocal quality.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Spasticity of pharyngeal muscles
MedGen UID:
342872
Concept ID:
C1853398
Finding
Spasticity of facial muscles
MedGen UID:
344036
Concept ID:
C1853404
Finding
Spasticity of one or more muscles innervated by the facial nerve.
Pseudobulbar affect
MedGen UID:
871239
Concept ID:
C4025720
Sign or Symptom
Pseudobulbar affect (PBA) is characterized by uncontrolled crying or laughing which may be disproportionate or inappropriate to the social context. Thus, there is a disparity between the patient's emotional expression and his or her emotional experience.
Abnormal upper motor neuron morphology
MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.
Decreased compound muscle action potential amplitude
MedGen UID:
908357
Concept ID:
C4230625
Finding
Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve.
Appendicular spasticity
MedGen UID:
937224
Concept ID:
C4313257
Finding
A type of spasticity that affects one or more limbs (arms or legs).
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Tongue muscle weakness
MedGen UID:
377897
Concept ID:
C1853406
Finding
Reduced strength of the tongue musculature, resulting in difficulties moving the tongue and possible accompanied by dysarthria or dysphagia.
Tongue spasticity
MedGen UID:
1053179
Concept ID:
CN378204
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the tongue.
Pallor
MedGen UID:
10547
Concept ID:
C0030232
Finding
Abnormally pale skin.
Saccadic smooth pursuit
MedGen UID:
373096
Concept ID:
C1836479
Finding
An abnormality of tracking eye movements in which smooth pursuit is interrupted by an abnormally high number of saccadic movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVJuvenile primary lateral sclerosis
Follow this link to review classifications for Juvenile primary lateral sclerosis in Orphanet.

Professional guidelines

PubMed

Sprute R, Jergas H, Ölmez A, Alawbathani S, Karasoy H, Dafsari HS, Becker K, Daimagüler HS, Nürnberg P, Muntoni F, Topaloglu H, Uyanik G, Cirak S
Am J Med Genet A 2021 Feb;185(2):344-354. Epub 2020 Nov 5 doi: 10.1002/ajmg.a.61951. PMID: 33155358

Recent clinical studies

Prognosis

Helal M, Mazaheri N, Shalbafan B, Malamiri RA, Dilaver N, Buchert R, Mohammadiasl J, Golchin N, Sedaghat A, Mehrjardi MYV, Haack TB, Riess O, Chung WK, Galehdari H, Shariati G, Maroofian R
Neurol Sci 2018 Nov;39(11):1917-1925. Epub 2018 Aug 21 doi: 10.1007/s10072-018-3526-8. PMID: 30128655
Hadano S, Kunita R, Otomo A, Suzuki-Utsunomiya K, Ikeda JE
Neurochem Int 2007 Jul-Sep;51(2-4):74-84. Epub 2007 May 4 doi: 10.1016/j.neuint.2007.04.010. PMID: 17566607
Millecamps S, Gentil BJ, Gros-Louis F, Rouleau G, Julien JP
Biochim Biophys Acta 2005 Aug 15;1745(1):84-100. Epub 2005 Jan 19 doi: 10.1016/j.bbamcr.2004.12.008. PMID: 16085057

Clinical prediction guides

Çobanoğlu G, Ozansoy M, Başak AN
Biochem Biophys Res Commun 2012 Oct 12;427(1):1-4. Epub 2012 Sep 7 doi: 10.1016/j.bbrc.2012.08.103. PMID: 22982304
Hadano S, Kunita R, Otomo A, Suzuki-Utsunomiya K, Ikeda JE
Neurochem Int 2007 Jul-Sep;51(2-4):74-84. Epub 2007 May 4 doi: 10.1016/j.neuint.2007.04.010. PMID: 17566607
Millecamps S, Gentil BJ, Gros-Louis F, Rouleau G, Julien JP
Biochim Biophys Acta 2005 Aug 15;1745(1):84-100. Epub 2005 Jan 19 doi: 10.1016/j.bbamcr.2004.12.008. PMID: 16085057

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