Amyotrophic Lateral Sclerosis Overview

Nailah Siddique, Teepu Siddique, Margaret P Adam, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya, Nailah Siddique, Teepu Siddique, Margaret P Adam, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya

Excerpt

The purpose of this overview is to increase the awareness of clinicians regarding genetic causes of amyotrophic lateral sclerosis (ALS) and related genetic counseling issues.

The following are the goals of this overview.

Goal 1: Describe the clinical characteristics of ALS.

Goal 2: Review genetic causes of ALS.

Goal 3: Provide an evaluation strategy to identify the genetic cause of ALS in a proband (when possible).

Goal 4: Inform genetic counseling of family members of an individual with ALS.

Goal 5: Provide a high-level view of management of ALS.

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References

Literature Cited

    1. Abrahams S, Goldstein LH, Suckling J, Ng V, Simmons A, Chitnis X, Atkins L, Williams SC, Leigh PN. Frontotemporal white matter changes in amyotrophic lateral sclerosis. J Neurol. 2005;252:321–31.
    1. Abrahams S, Newton J, Niven E, Foley J, Bak TH. Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:9–14.
    1. Akiyama T, Warita H, Kato M, Nishiyama A, Izumi R, Ikeda C, Kamada M, Suzuki N, Aoki M. Genotype-phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan. Muscle Nerve. 2016;54:398–404.
    1. Albert SM, Murphy PL, Del Bene ML, Rowland LP. A prospective study of preferences and actual treatment choices in ALS. Neurology. 1999;53:278–83.
    1. Al-Chalabi A, Calvo A, Chiò A, Colville S, Ellis CM, Hardiman O, Heverin M, Howard RS, Huisman MHB, Keren N, Leigh PN, Mazzini L, Mora G, Orrell RW, Rooney J, Scott KM, Scotton WJ, Seelen M, Shaw CE, Sidle KS, Swingler R, Tsuda M, Veldink JH, Visser AE, van den Berg LH, Pearce N. Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study. Lancet Neurol. 2014;13:1108–13.
    1. Al-Chalabi A, Fang F, Hanby MF, Leigh PN, Shaw CE, Ye W, Rijsdijk F. An estimate of amyotrophic lateral sclerosis heritability using twin data. J Neurol Neurosurg Psychiatry. 2010;81:1324–6.
    1. Andersen PM, Borasio GD, Dengler R, Hardiman O, Kollewe K, Leigh PN, Pradat PF, Silani V, Tomik B. EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol. 2005;12:921–38.
    1. Ashworth NL, Satkunam LE, Deforge D. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2004;1:CD004156
    1. Beeldman E, Raaphorst J, Klein Twennaar M, de Visser M, Schmand BA, de Haan RJ. The cognitive profile of ALS: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87:611–9.
    1. Belbasis L, Bellouu V, Evangelou E. Environmental risk factors and amyotrophic lateral sclerosis: an umbrella review and critical assessment of current evidence from systematic review and meta-analyses of observational studies. Neuroepidemiology. 2016;46:96–105.
    1. Bensimon G, Doble A. The tolerability of riluzole in the treatment of patients with amyotrophic lateral sclerosis. Expert Opin Drug Saf. 2004;3:525–34.
    1. Bigio EH. Making the diagnosis of frontotemporal lobar degeneration. Arch Pathol Lab Med. 2013;137:314–25.
    1. Borghero G, Pugliatti M, Marrosu MG, Floris G, Cannas A, Parish LD, Cua TB, Ticca A, Traccis S, Manera U, Canosa A, Moglia C, Calvo A, Barberis M, Brunetti M, Renton AE, Nails MA, Traynor BJ, Restagno G, Chiò A, et al. ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry. Neurobiol Aging. 2015;36:2906.e1–5.
    1. Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293–9.
    1. Brown RH, Jr, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377:162–72.
    1. Cameron A, Rosenfeld J. Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. Curr Opin Clin Nutr Metab Care. 2002;5:631–43.
    1. Chia R, Chiò A, Trayner BJ. Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications. Lancet Neurol. 2018;17:94–102.
    1. Chiò A, Calvo A, Moglia C, Ossala I, Brunetti M, Sbaiz L, Lai SL, Abramzon Y, Traynor BJ, Restagno G. A de novo missense mutation in the FUS gene in a "true" sporadic ALS case. Neurobiol Aging. 2011;32:553.e23–6.
    1. Cox PA, Richer R, Metcalf JS, Banack SA, Codd GA, Bradley WG. Cyanobacteria and BMAA exposure from desert dust: a possible link to sporadic ALS among Gulf War veterans. Amyotroph Lateral Scler. 2009;10 Suppl 2:109–17.
    1. de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto H, Nodera H, Shefner J, Swash M. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol. 2008;119:497–503.
    1. Farrero E, Prats E, Povedano M, Martinez-Matos JA, Manresa F, Escarrabill J. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement. Chest. 2005;127:2132–8.
    1. Goldstein LH, Adamson M, Jeffrey L, Down K, Barby T, Wilson C, Leigh PN. The psychological impact of MND on patients and carers. J Neurol Sci. 1998;160 Suppl 1:S114–21.
    1. Goutman SA. Diagnosis and clinical management of amyotrophic lateral sclerosis and other motor neuron disorders. Continuum. 2017;23:1332–59.
    1. Haley RW. Excess incidence of ALS in young Gulf War veterans. Neurology. 2003;61:750–6.
    1. Hardiman O, Al-Chalabi A, Chiò A, Logroscino G, Robberrecht W, Shaw PJ, Simmons Z, van den Berg LH. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071.
    1. Horner RD, Kamins KG, Feussner JR, Grambow SC, Hoff-Lindquist J, Harati Y, Mitsumoto H, Pascuzzi R, Spencer PS, Tim R, Howard D, Smith TC, Ryan MA, Coffman CJ, Kasarskis EJ. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology. 2003;61:742–9.
    1. Iacoangeli A, Al Khleifat A, Jones AR, Sproviero W, Shatunov A, Opie-Martin S, Morrison KE, Shaw PJ, Shaw CE, Fogh I, Dobson RJ, Newhouse SJ, Al-Chalabi A, et al. C9orf72 intermediate expansions of 24-30 repeats are associated with ALS. Acta Neuropathol Commun. 2019;7:115.
    1. 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, et al. Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis. JAMA Neurol. 2021;78:1236–48.
    1. Katz JS, Katzberg HD, Woolley SC, Marklund SL, Andersen PM. Combined fulminant frontotemporal dementia and amyotrophic lateral sclerosis associated with an I113T SOD1 mutation. Amyotroph Lateral Scler. 2012;13:567–9.
    1. Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, Marklund SL, Wyns S, Thijs V, Andersson J, van Marion I, Al-Chalabi A, Bornes S, Musson R, Hansen V, Beckman L, Adolfsson R, Pall HS, Prats H, Vermeire S, Rutgeerts P, Katayama S, Awata T, Leigh N, Lang-Lazdunski L, Dewerchin M, Shaw C, Moons L, Vlietinck R, Morrison KE, Robberecht W, Van Broeckhoven C, Collen D, Andersen PM, Carmeliet P. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet. 2003;34:383–94.
    1. Li YJ, Pericak-Vance MA, Haines JL, Siddique N, McKenna-Yasek D, Hung WY, Sapp P, Allen CI, Chen W, Hosler B, Saunders AM, Dellefave LM, Brown RH, Siddique T. Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis. Neurogenetics. 2004;5:209–13.
    1. Lopate G, Baloh RH, Al-Lozi MT, Miller TM, Fernandes Filho JA, Ni O, Leston A, Florence J, Schierbecker J, Allred P. Familial ALS with extreme phenotypic variability due to the I113T SOD1 mutation. Amyotroph Lateral Scler. 2010;11:232–6.
    1. Magnus T, Beck M, Giess R, Puls I, Naumann M, Toyka KV. Disease progression in amyotrophic lateral sclerosis: predictors of survival. Muscle Nerve. 2002;25:709–14.
    1. Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R, Borasio GD, Bradley WG, Bromberg MB, Brooks BR, Kasarskis EJ, Munsat TL, Oppenheimer EA. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology. 1999;52:1311–23.
    1. Montuschi A, Iazzolino B, Calvo A, Moglia C, Lopiano L, Restagno G, Brunetti M, Ossola I, Lo Presti A, Cammarosano S, Canosa A, Chiò A. Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy. J Neurol Neurosurg Psychiatry. 2015;86:168–73.
    1. Niven E, Newton J, Foley J, Colville S, Swingler R, Chandran S, Bak TH, Abrahams S. Validation of the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS): a cognitive tool for motor disorders. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:172–9.
    1. Ohta Y, Soucy G, Phaneuf D, Audet JN, Gros-Louis F, Rouleau GA, Blasco H, Corcia P, Andersen PM, Nordin F, Yamashita T, Abe K, Julien JP. Sex-dependent effects of chromogranin B P413L allelic variant as disease modifier in amyotrophic lateral sclerosis. Hum Mol Genet. 2016;25:4771–86.
    1. Orrell RW, Lane RJM, Ross M. Antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2007;24:CD002829
    1. Paillisse C, Lacomblez L, Dib M, Bensimon G, Garcia-Acosta S, Meininger V. Prognostic factors for survival in amyotrophic lateral sclerosis patients treated with riluzole. Amyotroph Lateral Scler Other Motor Neuron Disord. 2005;6:37–44.
    1. Raaphorst J, Beeldman E, De Visser M, De Haan RJ, Schmand B. A systematic review of behavioral changes in motor neuron disease. Amyotroph Lateral Scler. 2012;13:493–501.
    1. Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB, Turki SA, Dominiczak A, Morris A, Porteous D, Smith B, Stratton MR, Hurles ME, et al. Timing, rates and spectra of human germline mutation. Nat Genet. 2016;48:126–33.
    1. Riviere M, Meininger V, Zeisser P, Munsat T. An analysis of extended survival in patients with amyotrophic lateral sclerosis treated with riluzole. Arch Neurol. 1998;55:526–8.
    1. Ryan M, Heverin M, McLaughlin RL, Hardiman O. Lifetime risk and heritability of amyotrophic lateral sclerosis. JAMA Neurol. 2019a;76:1367–74.
    1. Ryan M, Zalvidar Vaillant T, McLaughlin RL, Doherty MA, Rooney J, Heverin M, Gutierrez J, Lara-Fernández GE, Pita Rodriguez M, Hackembruch J, Perna A, Vazquez MC, Musio M, Ketzoian CN, Logroscino G, Hardiman O. Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations. J Neurol Neurosurg Psychiatry. 2019b;90:659–65.
    1. Sawada H. Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis. Expert Opin Pharmacother. 2017;18:735–8.
    1. Saxon JA, Thompson JC, Jones M, Harris JM, Richardson AM, Langheinrich T, Neary D, Mann DM, Snowden JS. Examining the language and behavioural profile in FTD and ALS-FTD. J Neurol Neurosurg Psychiatry. 2017;88:675–80.
    1. Schreiber H, Gaigalat T, Wiedemuth-Catrinescu U, Graf M, Uttner I, Muche R, Ludolph AC. Cognitive function in bulbar- and spinal-onset amyotrophic lateral sclerosis. A longitudinal study in 52 patients. J Neurol. 2005;252:772–81.
    1. Strong MJ, Gordon PH. Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: discrete entities or spectrum? Amyotroph Lateral Scler Other Motor Neuron Disord. 2005;6:8–16.
    1. Tan HHG, Westening HJ, van der Burgh HK, van Es MA, Bakker LA, van Veenhuijzen K, van Eijk KR, van Eijk RPA, Veldink JH, van den Berg LH. The distinct traits of the UNC13A polymorphism in amyotrophic lateral sclerosis. Ann Neurol. 2020;88:796–806.
    1. van den Berg JP, de Groot IJ, Joha BC, van Haelst JM, van Gorcom P, Kalmijn S. Development and implementation of the Dutch protocol for rehabilitative management in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5:226–9.
    1. van Rheenen W, Shatunov A, Dekker AM, McLaughlin RL, Diekstra FP, Pulit SL, van der Spek RN, Vösa U, de Jong S, Robinson MR, et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016;48:1043–8.
    1. Woolley SC, York MK, Moore DH, Strutt AM, Murphy J, Schulz PE, Katz JS. Detecting frontotemporal dysfunction in ALS: utility of the ALS Cognitive Behavioral Screen (ALS-CBS). Amyotroph Lateral Scler. 2010;11:303–11.
Suggested Reading
    1. Abe K, Aoki M, Tsuji S, Itoyama Y, Sobue G, Togo M, Hamada C, Tanaka M, Akimoto M, Nakamura K, Takahashi F, Kondo K, Yoshino H, et al. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16:505–12.
    1. Andersen PM. Is all ALS genetic? Neurology. 2017;89:220–1.
    1. Ghasemi M, Brown RH., Jr Genetics of amyotrophic lateral sclerosis. Cold Spring Harb Perspect Med. 2018;8:a024125.
    1. Ly CV, Miller TM. Emerging antisense oligonucleotide and viral therapies for amyotrophic lateral sclerosis. Curr Opin Neurol. 2018;31:648–54.
    1. Oskarsson B, Gendron TF, Staff N. Amyotrophic lateral sclerosis: an update for 2018. Mayo Clin Proc. 2018;93:1617–28.
    1. Renaud L, Picher-Martel V, Codron P, Julien JP. Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol Commun. 2019;7:103.

Source: PubMed

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