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Abnormal upper motor neuron morphology

MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Synonym: Abnormal shape of upper motor neuron
 
HPO: HP:0002127

Definition

Any structural anomaly that affects the upper motor neuron. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Abnormal upper motor neuron morphology

Conditions with this feature

Adult polyglucosan body disease
MedGen UID:
342338
Concept ID:
C1849722
Disease or Syndrome
Most individuals with classic GBE1 adult polyglucosan body disease (GBE1-APBD) present after age 40 years with unexplained progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, autonomic dysfunction (associated with orthostatic hypotension and constipation), and mild cognitive difficulties (often executive dysfunction). Some affected individuals without classic GBE1-APBD have atypical phenotypes including Alzheimer disease-like dementia and axonal neuropathy, stroke-like episodes, and diaphragmatic failure; others may have a history of infantile liver disease.
Juvenile primary lateral sclerosis
MedGen UID:
342870
Concept ID:
C1853396
Disease or Syndrome
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.
Ataxia-hypogonadism-choroidal dystrophy syndrome
MedGen UID:
347798
Concept ID:
C1859093
Disease or Syndrome
PNPLA6 disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia; upper motor neuron involvement manifesting as spasticity and/or brisk reflexes; chorioretinal dystrophy associated with variable degrees of reduced visual function; and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). The hypogonadotropic hypogonadism occurs either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting); hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia); short stature; and impaired cognitive functioning (learning disabilities in children; deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia).
Amyotrophic lateral sclerosis type 2, juvenile
MedGen UID:
349246
Concept ID:
C1859807
Disease or Syndrome
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.
Primary lateral sclerosis, adult, 1
MedGen UID:
369357
Concept ID:
C1968845
Disease or Syndrome
Although primary lateral sclerosis (PLS) 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 were 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. See 606353 for autosomal recessive juvenile-onset PLS, which is caused by mutations in the ALS2 gene (606352).
Amyotrophic lateral sclerosis type 21
MedGen UID:
813851
Concept ID:
C3807521
Disease or Syndrome
Amyotrophic lateral sclerosis-21 (ALS21) is an autosomal dominant neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia (summary by Johnson et al., 2014). For a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400).
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1
MedGen UID:
1648386
Concept ID:
C4721893
Disease or Syndrome
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: 1. The latent stage is characterized by normal early development. 2. The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. 3. In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social problems. 4. The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years.
Hereditary spastic paraplegia 9A
MedGen UID:
1800401
Concept ID:
C5568978
Disease or Syndrome
Autosomal dominant spastic paraplegia-9A is a neurologic disorder characterized by onset of slowly progressive spasticity mainly affecting the lower limbs. The age at onset usually ranges from adolescence to adulthood, and patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency (summary by Coutelier et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).

Professional guidelines

PubMed

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Recent clinical studies

Etiology

Anand T, Ishaque A, Ta D, Khan MU, Bharti K, Wu A, Krebs D, Beaulieu C, Seres P, Kalra S
Brain Behav 2023 Jul;13(7):e3102. Epub 2023 Jun 6 doi: 10.1002/brb3.3102. PMID: 37279166Free PMC Article
Ding G, Fan Y
Comput Math Methods Med 2022;2022:3907751. Epub 2022 Oct 12 doi: 10.1155/2022/3907751. PMID: 36276994Free PMC Article
Vogrig A, Joubert B, Maureille A, Thomas L, Bernard E, Streichenberger N, Cotton F, Ducray F, Honnorat J
J Neurol 2019 Feb;266(2):398-410. Epub 2018 Nov 29 doi: 10.1007/s00415-018-9143-x. PMID: 30498914
Blackstone C
Handb Clin Neurol 2018;148:633-652. doi: 10.1016/B978-0-444-64076-5.00041-7. PMID: 29478605
Grieve SM, Menon P, Korgaonkar MS, Gomes L, Foster S, Kiernan MC, Vucic S
Amyotroph Lateral Scler Frontotemporal Degener 2015;17(1-2):85-92. Epub 2015 Oct 12 doi: 10.3109/21678421.2015.1074707. PMID: 26458122

Diagnosis

Tetter S, Arseni D, Murzin AG, Buhidma Y, Peak-Chew SY, Garringer HJ, Newell KL, Vidal R, Apostolova LG, Lashley T, Ghetti B, Ryskeldi-Falcon B
Nature 2024 Jan;625(7994):345-351. Epub 2023 Dec 6 doi: 10.1038/s41586-023-06801-2. PMID: 38057661Free PMC Article
Xie M, Pallegar PN, Parusel S, Nguyen AT, Wu LJ
Mol Neurodegener 2023 Oct 19;18(1):75. doi: 10.1186/s13024-023-00665-w. PMID: 37858176Free PMC Article
Jaiser SR, Mitra D, Williams TL, Baker MR
J Neurol 2019 Mar;266(3):667-679. Epub 2019 Jan 10 doi: 10.1007/s00415-019-09186-3. PMID: 30631918Free PMC Article
Zheng Q, Chu L, Tan L, Zhang H
Neurol Sci 2016 Dec;37(12):1905-1909. Epub 2016 Jul 29 doi: 10.1007/s10072-016-2686-7. PMID: 27473302
Hentati F, Hentati E, Amouri R
Handb Clin Neurol 2013;115:933-8. doi: 10.1016/B978-0-444-52902-2.00052-7. PMID: 23931822

Therapy

Ding G, Fan Y
Comput Math Methods Med 2022;2022:3907751. Epub 2022 Oct 12 doi: 10.1155/2022/3907751. PMID: 36276994Free PMC Article
Ta D, Ishaque A, Srivastava O, Hanstock C, Seres P, Eurich DT, Luk C, Briemberg H, Frayne R, Genge AL, Graham SJ, Korngut L, Zinman L, Kalra S
Neurology 2021 Aug 24;97(8):e803-e813. Epub 2021 Jun 14 doi: 10.1212/WNL.0000000000012367. PMID: 34426551Free PMC Article
Cruz-Martinez A, Arpa J, Palau F
J Peripher Nerv Syst 2000 Jun;5(2):101-5. doi: 10.1046/j.1529-8027.2000.00007.x. PMID: 10905469
Ono S, Imai T, Munakata S, Takahashi K, Kanda F, Hashimoto K, Yamano T, Shimizu N, Nagao K, Yamauchi M
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Pioro EP, Antel JP, Cashman NR, Arnold DL
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Prognosis

Takeda T, Iijima M, Seki M, Higuchi E, Shimizu Y, Shibata N, Kitagawa K
Clin Neuropathol 2022 Jul-Aug;41(4):157-161. doi: 10.5414/NP301438. PMID: 35343426
Lenglet T, Camdessanché JP
Rev Neurol (Paris) 2017 May;173(5):280-287. Epub 2017 Apr 28 doi: 10.1016/j.neurol.2017.04.003. PMID: 28461025
Zheng Q, Chu L, Tan L, Zhang H
Neurol Sci 2016 Dec;37(12):1905-1909. Epub 2016 Jul 29 doi: 10.1007/s10072-016-2686-7. PMID: 27473302
Hentati F, Hentati E, Amouri R
Handb Clin Neurol 2013;115:933-8. doi: 10.1016/B978-0-444-52902-2.00052-7. PMID: 23931822
Finsterer J
J Neurol Sci 2010 Nov 15;298(1-2):1-10. Epub 2010 Sep 16 doi: 10.1016/j.jns.2010.08.025. PMID: 20846673

Clinical prediction guides

Xie M, Pallegar PN, Parusel S, Nguyen AT, Wu LJ
Mol Neurodegener 2023 Oct 19;18(1):75. doi: 10.1186/s13024-023-00665-w. PMID: 37858176Free PMC Article
van Hummel A, Sabale M, Przybyla M, van der Hoven J, Chan G, Feiten AF, Chung RS, Ittner LM, Ke YD
Neuropathol Appl Neurobiol 2023 Apr;49(2):e12902. doi: 10.1111/nan.12902. PMID: 36951214Free PMC Article
Ishihara K, Fukui T, Kawamura M, Shiota JI, Nakano I
Neuropathology 2023 Feb;43(1):27-43. Epub 2022 Nov 3 doi: 10.1111/neup.12854. PMID: 36328774
Takeda T, Iijima M, Seki M, Higuchi E, Shimizu Y, Shibata N, Kitagawa K
Clin Neuropathol 2022 Jul-Aug;41(4):157-161. doi: 10.5414/NP301438. PMID: 35343426
Vogrig A, Joubert B, Maureille A, Thomas L, Bernard E, Streichenberger N, Cotton F, Ducray F, Honnorat J
J Neurol 2019 Feb;266(2):398-410. Epub 2018 Nov 29 doi: 10.1007/s00415-018-9143-x. PMID: 30498914

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