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Amyotrophic lateral sclerosis, susceptibility to, 25(ALS25)

MedGen UID:
1633917
Concept ID:
C4693609
Finding
Synonyms: ALS25; AMYOTROPHIC LATERAL SCLEROSIS, SUSCEPTIBILITY TO, 25
 
Gene (location): KIF5A (12q13.3)
 
Monarch Initiative: MONDO:0060670
OMIM®: 617921

Definition

Amyotrophic lateral sclerosis is a neurodegenerative disorder clinically characterized by rapidly progressive muscle weakness and death due to respiratory failure. ALS25 may have a lower median age at onset (46.5 years) and longer median survival (10 years) than that found in epidemiologic studies (62.5 years and 20 to 30 months, respectively) (Nicolas et al., 2018). [from OMIM]

Clinical features

From HPO
Amyotrophic lateral sclerosis
MedGen UID:
274
Concept ID:
C0002736
Disease or Syndrome
Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.\n\nThere are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.\n\nThe first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.\n\nApproximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.\n\nA rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms.

Professional guidelines

PubMed

Al-Chalabi A, van den Berg LH, Veldink J
Nat Rev Neurol 2017 Feb;13(2):96-104. Epub 2016 Dec 16 doi: 10.1038/nrneurol.2016.182. PMID: 27982040
Alavi A, Nafissi S, Rohani M, Zamani B, Sedighi B, Shamshiri H, Fan JB, Ronaghi M, Elahi E
Neurobiol Aging 2013 May;34(5):1516.e1-8. Epub 2012 Oct 9 doi: 10.1016/j.neurobiolaging.2012.09.006. PMID: 23062701
Gordon PH
CNS Drugs 2011 Jan;25(1):1-15. doi: 10.2165/11586000-000000000-00000. PMID: 21128691

Recent clinical studies

Etiology

Chang CY, Ting HC, Liu CA, Su HL, Chiou TW, Lin SZ, Harn HJ, Ho TJ
Molecules 2020 Apr 24;25(8) doi: 10.3390/molecules25082000. PMID: 32344649Free PMC Article
Nowicka N, Juranek J, Juranek JK, Wojtkiewicz J
Int J Mol Sci 2019 May 28;20(11) doi: 10.3390/ijms20112616. PMID: 31141951Free PMC Article
Acosta-Cabronero J, Machts J, Schreiber S, Abdulla S, Kollewe K, Petri S, Spotorno N, Kaufmann J, Heinze HJ, Dengler R, Vielhaber S, Nestor PJ
Radiology 2018 Oct;289(1):195-203. Epub 2018 Jul 24 doi: 10.1148/radiol.2018180112. PMID: 30040038Free PMC Article
Al-Chalabi A, van den Berg LH, Veldink J
Nat Rev Neurol 2017 Feb;13(2):96-104. Epub 2016 Dec 16 doi: 10.1038/nrneurol.2016.182. PMID: 27982040
Gordon PH
CNS Drugs 2011 Jan;25(1):1-15. doi: 10.2165/11586000-000000000-00000. PMID: 21128691

Diagnosis

Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, Alahmady N, Renton AE, Topp SD, Gibbs JR, Cookson MR, Sabir MS, Dalgard CL, Troakes C, Jones AR, Shatunov A, Iacoangeli A, Al Khleifat A, Ticozzi N, Silani V, Gellera C, Blair IP, Dobson-Stone C, Kwok JB, Bonkowski ES, Palvadeau R, Tienari PJ, Morrison KE, Shaw PJ, Al-Chalabi A, Brown RH Jr, Calvo A, Mora G, Al-Saif H, Gotkine M, Leigh F, Chang IJ, Perlman SJ, Glass I, Scott AI, Shaw CE, Basak AN, Landers JE, Chiò A, Crawford TO, Smith BN, Traynor BJ; FALS Sequencing Consortium; American Genome Center; International ALS Genomics Consortium; and ITALSGEN Consortium, Smith BN, Ticozzi N, Fallini C, Gkazi AS, Topp SD, Scotter EL, Kenna KP, Keagle P, Tiloca C, Vance C, Troakes C, Colombrita C, King A, Pensato V, Castellotti B, Baas F, Ten Asbroek ALMA, McKenna-Yasek D, McLaughlin RL, Polak M, Asress S, Esteban-Pérez J, Stevic Z, D'Alfonso S, Mazzini L, Comi GP, Del Bo R, Ceroni M, Gagliardi S, Querin G, Bertolin C, van Rheenen W, Rademakers R, van Blitterswijk M, Lauria G, Duga S, Corti S, Cereda C, Corrado L, Sorarù G, Williams KL, Nicholson GA, Blair IP, Leblond-Manry C, Rouleau GA, Hardiman O, Morrison KE, Veldink JH, van den Berg LH, Al-Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, García-Redondo A, Wu Z, Glass JD, Gellera C, Ratti A, Brown RH Jr, Silani V, Shaw CE, Landers JE, Dalgard CL, Adeleye A, Soltis AR, Alba C, Viollet C, Bacikova D, Hupalo DN, Sukumar G, Pollard HB, Wilkerson MD, Martinez EM, Abramzon Y, Ahmed S, Arepalli S, Baloh RH, Bowser R, Brady CB, Brice A, Broach J, Campbell RH, Camu W, Chia R, Cooper-Knock J, Ding J, Drepper C, Drory VE, Dunckley TL, Eicher JD, England BK, Faghri F, Feldman E, Floeter MK, Fratta P, Geiger JT, Gerhard G, Gibbs JR, Gibson SB, Glass JD, Hardy J, Harms MB, Heiman-Patterson TD, Hernandez DG, Jansson L, Kirby J, Kowall NW, Laaksovirta H, Landeck N, Landi F, Le Ber I, Lumbroso S, MacGowan DJL, Maragakis NJ, Mora G, Mouzat K, Murphy NA, Myllykangas L, Nalls MA, Orrell RW, Ostrow LW, Pamphlett R, Pickering-Brown S, Pioro EP, Pletnikova O, Pliner HA, Pulst SM, Ravits JM, Renton AE, Rivera A, Robberecht W, Rogaeva E, Rollinson S, Rothstein JD, Scholz SW, Sendtner M, Shaw PJ, Sidle KC, Simmons Z, Singleton AB, Smith N, Stone DJ, Tienari PJ, Troncoso JC, Valori M, Van Damme P, Van Deerlin VM, Van Den Bosch L, Zinman L, Landers JE, Chiò A, Traynor BJ, Angelocola SM, Ausiello FP, Barberis M, Bartolomei I, Battistini S, Bersano E, Bisogni G, Borghero G, Brunetti M, Cabona C, Calvo A, Canale F, Canosa A, Cantisani TA, Capasso M, Caponnetto C, Cardinali P, Carrera P, Casale F, Chiò A, Colletti T, Conforti FL, Conte A, Conti E, Corbo M, Cuccu S, Dalla Bella E, D'Errico E, DeMarco G, Dubbioso R, Ferrarese C, Ferraro PM, Filippi M, Fini N, Floris G, Fuda G, Gallone S, Gianferrari G, Giannini F, Grassano M, Greco L, Iazzolino B, Introna A, La Bella V, Lattante S, Lauria G, Liguori R, Logroscino G, Logullo FO, Lunetta C, Mandich P, Mandrioli J, Manera U, Manganelli F, Marangi G, Marinou K, Marrosu MG, Martinelli I, Messina S, Moglia C, Mora G, Mosca L, Murru MR, Origone P, Passaniti C, Petrelli C, Petrucci A, Pozzi S, Pugliatti M, Quattrini A, Ricci C, Riolo G, Riva N, Russo M, Sabatelli M, Salamone P, Salivetto M, Salvi F, Santarelli M, Sbaiz L, Sideri R, Simone I, Simonini C, Spataro R, Tanel R, Tedeschi G, Ticca A, Torriello A, Tranquilli S, Tremolizzo L, Trojsi F, Vasta R, Vacchiano V, Vita G, Volanti P, Zollino M, Zucchi E
JAMA Neurol 2021 Oct 1;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598. PMID: 34459874Free PMC Article
Acosta-Cabronero J, Machts J, Schreiber S, Abdulla S, Kollewe K, Petri S, Spotorno N, Kaufmann J, Heinze HJ, Dengler R, Vielhaber S, Nestor PJ
Radiology 2018 Oct;289(1):195-203. Epub 2018 Jul 24 doi: 10.1148/radiol.2018180112. PMID: 30040038Free PMC Article
Al-Chalabi A, van den Berg LH, Veldink J
Nat Rev Neurol 2017 Feb;13(2):96-104. Epub 2016 Dec 16 doi: 10.1038/nrneurol.2016.182. PMID: 27982040
Andersen PM, Al-Chalabi A
Nat Rev Neurol 2011 Oct 11;7(11):603-15. doi: 10.1038/nrneurol.2011.150. PMID: 21989245
Gordon PH
CNS Drugs 2011 Jan;25(1):1-15. doi: 10.2165/11586000-000000000-00000. PMID: 21128691

Therapy

Benatar M, Wuu J, Turner MR
Brain 2023 Jul 3;146(7):2711-2716. doi: 10.1093/brain/awac394. PMID: 36310538Free PMC Article
Larsson SC, Roos PM
Neurobiol Aging 2020 Mar;87:140.e1-140.e3. Epub 2019 Nov 6 doi: 10.1016/j.neurobiolaging.2019.10.024. PMID: 31785838
Acosta-Cabronero J, Machts J, Schreiber S, Abdulla S, Kollewe K, Petri S, Spotorno N, Kaufmann J, Heinze HJ, Dengler R, Vielhaber S, Nestor PJ
Radiology 2018 Oct;289(1):195-203. Epub 2018 Jul 24 doi: 10.1148/radiol.2018180112. PMID: 30040038Free PMC Article
Seelen M, Toro Campos RA, Veldink JH, Visser AE, Hoek G, Brunekreef B, van der Kooi AJ, de Visser M, Raaphorst J, van den Berg LH, Vermeulen RCH
Environ Health Perspect 2017 Sep 27;125(9):097023. doi: 10.1289/EHP1115. PMID: 29989551Free PMC Article
Gordon PH
CNS Drugs 2011 Jan;25(1):1-15. doi: 10.2165/11586000-000000000-00000. PMID: 21128691

Prognosis

Benatar M, Wuu J, Turner MR
Brain 2023 Jul 3;146(7):2711-2716. doi: 10.1093/brain/awac394. PMID: 36310538Free PMC Article
Yang T, Hou Y, Li C, Cao B, Cheng Y, Wei Q, Zhang L, Shang H
J Neurol Neurosurg Psychiatry 2021 Jul;92(7):688-693. Epub 2021 Feb 9 doi: 10.1136/jnnp-2020-325701. PMID: 33563800
Larsson SC, Roos PM
Neurobiol Aging 2020 Mar;87:140.e1-140.e3. Epub 2019 Nov 6 doi: 10.1016/j.neurobiolaging.2019.10.024. PMID: 31785838
Donatelli G, Caldarazzo Ienco E, Costagli M, Migaleddu G, Cecchi P, Siciliano G, Cosottini M
Neuroimage Clin 2019;24:101934. Epub 2019 Jul 15 doi: 10.1016/j.nicl.2019.101934. PMID: 31377555Free PMC Article
Körner S, Kollewe K, Ilsemann J, Müller-Heine A, Dengler R, Krampfl K, Petri S
Eur J Neurol 2013 Apr;20(4):647-54. Epub 2012 Oct 25 doi: 10.1111/ene.12015. PMID: 23094606

Clinical prediction guides

Benatar M, Wuu J, Turner MR
Brain 2023 Jul 3;146(7):2711-2716. doi: 10.1093/brain/awac394. PMID: 36310538Free PMC Article
Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, Alahmady N, Renton AE, Topp SD, Gibbs JR, Cookson MR, Sabir MS, Dalgard CL, Troakes C, Jones AR, Shatunov A, Iacoangeli A, Al Khleifat A, Ticozzi N, Silani V, Gellera C, Blair IP, Dobson-Stone C, Kwok JB, Bonkowski ES, Palvadeau R, Tienari PJ, Morrison KE, Shaw PJ, Al-Chalabi A, Brown RH Jr, Calvo A, Mora G, Al-Saif H, Gotkine M, Leigh F, Chang IJ, Perlman SJ, Glass I, Scott AI, Shaw CE, Basak AN, Landers JE, Chiò A, Crawford TO, Smith BN, Traynor BJ; FALS Sequencing Consortium; American Genome Center; International ALS Genomics Consortium; and ITALSGEN Consortium, Smith BN, Ticozzi N, Fallini C, Gkazi AS, Topp SD, Scotter EL, Kenna KP, Keagle P, Tiloca C, Vance C, Troakes C, Colombrita C, King A, Pensato V, Castellotti B, Baas F, Ten Asbroek ALMA, McKenna-Yasek D, McLaughlin RL, Polak M, Asress S, Esteban-Pérez J, Stevic Z, D'Alfonso S, Mazzini L, Comi GP, Del Bo R, Ceroni M, Gagliardi S, Querin G, Bertolin C, van Rheenen W, Rademakers R, van Blitterswijk M, Lauria G, Duga S, Corti S, Cereda C, Corrado L, Sorarù G, Williams KL, Nicholson GA, Blair IP, Leblond-Manry C, Rouleau GA, Hardiman O, Morrison KE, Veldink JH, van den Berg LH, Al-Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, García-Redondo A, Wu Z, Glass JD, Gellera C, Ratti A, Brown RH Jr, Silani V, Shaw CE, Landers JE, Dalgard CL, Adeleye A, Soltis AR, Alba C, Viollet C, Bacikova D, Hupalo DN, Sukumar G, Pollard HB, Wilkerson MD, Martinez EM, Abramzon Y, Ahmed S, Arepalli S, Baloh RH, Bowser R, Brady CB, Brice A, Broach J, Campbell RH, Camu W, Chia R, Cooper-Knock J, Ding J, Drepper C, Drory VE, Dunckley TL, Eicher JD, England BK, Faghri F, Feldman E, Floeter MK, Fratta P, Geiger JT, Gerhard G, Gibbs JR, Gibson SB, Glass JD, Hardy J, Harms MB, Heiman-Patterson TD, Hernandez DG, Jansson L, Kirby J, Kowall NW, Laaksovirta H, Landeck N, Landi F, Le Ber I, Lumbroso S, MacGowan DJL, Maragakis NJ, Mora G, Mouzat K, Murphy NA, Myllykangas L, Nalls MA, Orrell RW, Ostrow LW, Pamphlett R, Pickering-Brown S, Pioro EP, Pletnikova O, Pliner HA, Pulst SM, Ravits JM, Renton AE, Rivera A, Robberecht W, Rogaeva E, Rollinson S, Rothstein JD, Scholz SW, Sendtner M, Shaw PJ, Sidle KC, Simmons Z, Singleton AB, Smith N, Stone DJ, Tienari PJ, Troncoso JC, Valori M, Van Damme P, Van Deerlin VM, Van Den Bosch L, Zinman L, Landers JE, Chiò A, Traynor BJ, Angelocola SM, Ausiello FP, Barberis M, Bartolomei I, Battistini S, Bersano E, Bisogni G, Borghero G, Brunetti M, Cabona C, Calvo A, Canale F, Canosa A, Cantisani TA, Capasso M, Caponnetto C, Cardinali P, Carrera P, Casale F, Chiò A, Colletti T, Conforti FL, Conte A, Conti E, Corbo M, Cuccu S, Dalla Bella E, D'Errico E, DeMarco G, Dubbioso R, Ferrarese C, Ferraro PM, Filippi M, Fini N, Floris G, Fuda G, Gallone S, Gianferrari G, Giannini F, Grassano M, Greco L, Iazzolino B, Introna A, La Bella V, Lattante S, Lauria G, Liguori R, Logroscino G, Logullo FO, Lunetta C, Mandich P, Mandrioli J, Manera U, Manganelli F, Marangi G, Marinou K, Marrosu MG, Martinelli I, Messina S, Moglia C, Mora G, Mosca L, Murru MR, Origone P, Passaniti C, Petrelli C, Petrucci A, Pozzi S, Pugliatti M, Quattrini A, Ricci C, Riolo G, Riva N, Russo M, Sabatelli M, Salamone P, Salivetto M, Salvi F, Santarelli M, Sbaiz L, Sideri R, Simone I, Simonini C, Spataro R, Tanel R, Tedeschi G, Ticca A, Torriello A, Tranquilli S, Tremolizzo L, Trojsi F, Vasta R, Vacchiano V, Vita G, Volanti P, Zollino M, Zucchi E
JAMA Neurol 2021 Oct 1;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598. PMID: 34459874Free PMC Article
Larsson SC, Roos PM
Neurobiol Aging 2020 Mar;87:140.e1-140.e3. Epub 2019 Nov 6 doi: 10.1016/j.neurobiolaging.2019.10.024. PMID: 31785838
Al-Chalabi A, van den Berg LH, Veldink J
Nat Rev Neurol 2017 Feb;13(2):96-104. Epub 2016 Dec 16 doi: 10.1038/nrneurol.2016.182. PMID: 27982040
Andersen PM, Al-Chalabi A
Nat Rev Neurol 2011 Oct 11;7(11):603-15. doi: 10.1038/nrneurol.2011.150. PMID: 21989245

Recent systematic reviews

Yang T, Hou Y, Li C, Cao B, Cheng Y, Wei Q, Zhang L, Shang H
J Neurol Neurosurg Psychiatry 2021 Jul;92(7):688-693. Epub 2021 Feb 9 doi: 10.1136/jnnp-2020-325701. PMID: 33563800
Wei Q, Chen X, Chen Y, Ou R, Cao B, Hou Y, Zhang L, Shang HF
Sci China Life Sci 2019 Apr;62(4):517-525. Epub 2019 Mar 7 doi: 10.1007/s11427-018-9453-x. PMID: 30863961

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