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Amyotrophic lateral sclerosis type 11(ALS11)

MedGen UID:
393399
Concept ID:
C2675491
Disease or Syndrome
Synonyms: ALS11; FIG4-Related Amyotrophic Lateral Sclerosis
 
Gene (location): FIG4 (6q21)
 
Monarch Initiative: MONDO:0012945
OMIM®: 612577

Definition

An autosomal dominant form of amyotrophic lateral sclerosis caused by mutation(s) in the FIG4 gene, encoding polyphosphoinositide phosphatase. [from NCI]

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.
Upper motor neuron dysfunction
MedGen UID:
333241
Concept ID:
C1839042
Pathologic Function
A functional anomaly of the upper motor neuron. The upper motor neurons are neurons of the primary motor cortex which project to the brainstem and spinal chord via the corticonuclear, corticobulbar and corticospinal (pyramidal) tracts. They are involved in control of voluntary movements. Dysfunction leads to weakness, impairment of fine motor movements, spasticity, hyperreflexia and abnormal pyramidal signs.
Bulbar signs
MedGen UID:
347246
Concept ID:
C1856507
Finding
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Somatic sensory dysfunction
MedGen UID:
1790456
Concept ID:
C5551413
Finding
An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).

Professional guidelines

PubMed

James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Wadman RI, van der Pol WL, Bosboom WM, Asselman FL, van den Berg LH, Iannaccone ST, Vrancken AF
Cochrane Database Syst Rev 2020 Jan 6;1(1):CD006282. doi: 10.1002/14651858.CD006282.pub5. PMID: 32006461Free PMC Article
Nakken O, Sørum L, Holmøy T
Tidsskr Nor Laegeforen 2018 Sep 4;138(13) Epub 2018 Sep 3 doi: 10.4045/tidsskr.18.0193. PMID: 30180501

Curated

Orphanet, Amyotrophic lateral sclerosis, 2007

Recent clinical studies

Etiology

Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
Ge YJ, Ou YN, Deng YT, Wu BS, Yang L, Zhang YR, Chen SD, Huang YY, Dong Q, Tan L, Yu JT; International FTD-Genomics Consortium
Biol Psychiatry 2023 May 1;93(9):770-779. Epub 2022 Nov 9 doi: 10.1016/j.biopsych.2022.11.002. PMID: 36759259
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Chen H, Zhang J, Wang T, Zhang S, Lai Q, Huang S, Zeng P
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4497-e4508. doi: 10.1210/clinem/dgab465. PMID: 34171091
Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A; ITALSGEN Consortium, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L; Genomic Translation for ALS Care (GTAC) Consortium, Moreno CAM, Kamalakaran S, Goldstein DB; ALS Sequencing Consortium, Gitler AD, Harris T, Myers RM; NYGC ALS Consortium, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC; Answer ALS Foundation, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E; Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J; SLAGEN Consortium, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C; French ALS Consortium, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, Sidle KC, Malaspina A, Hardy J, Singleton AB, Johnson JO, Arepalli S, Sapp PC, McKenna-Yasek D, Polak M, Asress S, Al-Sarraj S, King A, Troakes C, Vance C, de Belleroche J, Baas F, Ten Asbroek ALMA, Muñoz-Blanco JL, Hernandez DG, Ding J, Gibbs JR, Scholz SW, Floeter MK, Campbell RH, Landi F, Bowser R, Pulst SM, Ravits JM, MacGowan DJL, Kirby J, Pioro EP, Pamphlett R, Broach J, Gerhard G, Dunckley TL, Brady CB, Kowall NW, Troncoso JC, Le Ber I, Mouzat K, Lumbroso S, Heiman-Patterson TD, Kamel F, Van Den Bosch L, Baloh RH, Strom TM, Meitinger T, Shatunov A, Van Eijk KR, de Carvalho M, Kooyman M, Middelkoop B, Moisse M, McLaughlin RL, Van Es MA, Weber M, Boylan KB, Van Blitterswijk M, Rademakers R, Morrison KE, Basak AN, Mora JS, Drory VE, Shaw PJ, Turner MR, Talbot K, Hardiman O, Williams KL, Fifita JA, Nicholson GA, Blair IP, Rouleau GA, Esteban-Pérez J, García-Redondo A, Al-Chalabi A; Project MinE ALS Sequencing Consortium, Rogaeva E, Zinman L, Ostrow LW, Maragakis NJ, Rothstein JD, Simmons Z, Cooper-Knock J, Brice A, Goutman SA, Feldman EL, Gibson SB, Taroni F, Ratti A, Gellera C, Van Damme P, Robberecht W, Fratta P, Sabatelli M, Lunetta C, Ludolph AC, Andersen PM, Weishaupt JH, Camu W, Trojanowski JQ, Van Deerlin VM, Brown RH Jr, van den Berg LH, Veldink JH, Harms MB, Glass JD, Stone DJ, Tienari P, Silani V, Chiò A, Shaw CE, Traynor BJ, Landers JE
Neuron 2018 Mar 21;97(6):1268-1283.e6. doi: 10.1016/j.neuron.2018.02.027. PMID: 29566793Free PMC Article

Diagnosis

Ge YJ, Ou YN, Deng YT, Wu BS, Yang L, Zhang YR, Chen SD, Huang YY, Dong Q, Tan L, Yu JT; International FTD-Genomics Consortium
Biol Psychiatry 2023 May 1;93(9):770-779. Epub 2022 Nov 9 doi: 10.1016/j.biopsych.2022.11.002. PMID: 36759259
Donohue C, Gray LT, Anderson A, DiBiase L, Wymer JP, Plowman EK
J Speech Lang Hear Res 2023 Jan 12;66(1):154-162. Epub 2022 Dec 16 doi: 10.1044/2022_JSLHR-22-00312. PMID: 36525626Free PMC Article
Mirzalieva O, Juncker M, Schwartzenburg J, Desai S
Cells 2022 Feb 4;11(3) doi: 10.3390/cells11030538. PMID: 35159348Free PMC Article
Puopolo M, Bacigalupo I, Piscopo P, Lacorte E, Di Pucchio A, Santarelli M, Inghilleri M, Petrucci A, Sabatelli M; Latium Registry Group, Vanacore N
Brain Behav 2021 Dec;11(12):e2378. Epub 2021 Oct 30 doi: 10.1002/brb3.2378. PMID: 34716673Free PMC Article
Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A; ITALSGEN Consortium, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L; Genomic Translation for ALS Care (GTAC) Consortium, Moreno CAM, Kamalakaran S, Goldstein DB; ALS Sequencing Consortium, Gitler AD, Harris T, Myers RM; NYGC ALS Consortium, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC; Answer ALS Foundation, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E; Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J; SLAGEN Consortium, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C; French ALS Consortium, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, Sidle KC, Malaspina A, Hardy J, Singleton AB, Johnson JO, Arepalli S, Sapp PC, McKenna-Yasek D, Polak M, Asress S, Al-Sarraj S, King A, Troakes C, Vance C, de Belleroche J, Baas F, Ten Asbroek ALMA, Muñoz-Blanco JL, Hernandez DG, Ding J, Gibbs JR, Scholz SW, Floeter MK, Campbell RH, Landi F, Bowser R, Pulst SM, Ravits JM, MacGowan DJL, Kirby J, Pioro EP, Pamphlett R, Broach J, Gerhard G, Dunckley TL, Brady CB, Kowall NW, Troncoso JC, Le Ber I, Mouzat K, Lumbroso S, Heiman-Patterson TD, Kamel F, Van Den Bosch L, Baloh RH, Strom TM, Meitinger T, Shatunov A, Van Eijk KR, de Carvalho M, Kooyman M, Middelkoop B, Moisse M, McLaughlin RL, Van Es MA, Weber M, Boylan KB, Van Blitterswijk M, Rademakers R, Morrison KE, Basak AN, Mora JS, Drory VE, Shaw PJ, Turner MR, Talbot K, Hardiman O, Williams KL, Fifita JA, Nicholson GA, Blair IP, Rouleau GA, Esteban-Pérez J, García-Redondo A, Al-Chalabi A; Project MinE ALS Sequencing Consortium, Rogaeva E, Zinman L, Ostrow LW, Maragakis NJ, Rothstein JD, Simmons Z, Cooper-Knock J, Brice A, Goutman SA, Feldman EL, Gibson SB, Taroni F, Ratti A, Gellera C, Van Damme P, Robberecht W, Fratta P, Sabatelli M, Lunetta C, Ludolph AC, Andersen PM, Weishaupt JH, Camu W, Trojanowski JQ, Van Deerlin VM, Brown RH Jr, van den Berg LH, Veldink JH, Harms MB, Glass JD, Stone DJ, Tienari P, Silani V, Chiò A, Shaw CE, Traynor BJ, Landers JE
Neuron 2018 Mar 21;97(6):1268-1283.e6. doi: 10.1016/j.neuron.2018.02.027. PMID: 29566793Free PMC Article

Therapy

Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
Ge YJ, Ou YN, Deng YT, Wu BS, Yang L, Zhang YR, Chen SD, Huang YY, Dong Q, Tan L, Yu JT; International FTD-Genomics Consortium
Biol Psychiatry 2023 May 1;93(9):770-779. Epub 2022 Nov 9 doi: 10.1016/j.biopsych.2022.11.002. PMID: 36759259
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Chen H, Zhang J, Wang T, Zhang S, Lai Q, Huang S, Zeng P
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4497-e4508. doi: 10.1210/clinem/dgab465. PMID: 34171091
Fuke N, Nagata N, Suganuma H, Ota T
Nutrients 2019 Sep 23;11(10) doi: 10.3390/nu11102277. PMID: 31547555Free PMC Article

Prognosis

Chiò A, Moglia C, Canosa A, Manera U, Grassano M, Vasta R, Palumbo F, Gallone S, Brunetti M, Barberis M, De Marchi F, Dalgard C, Chia R, Mora G, Iazzolino B, Peotta L, Traynor BJ, Corrado L, D'Alfonso S, Mazzini L, Calvo A
Neurology 2023 Jul 4;101(1):e83-e93. Epub 2023 May 18 doi: 10.1212/WNL.0000000000207367. PMID: 37202167Free PMC Article
Skajaa N, Riahi EB, Szépligeti SK, Horváth-Puhó E, Sørensen TT, Henderson VW, Sørensen HT
Brain Behav 2023 Jun;13(6):e3007. Epub 2023 Apr 19 doi: 10.1002/brb3.3007. PMID: 37073502Free PMC Article
Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
Mirzalieva O, Juncker M, Schwartzenburg J, Desai S
Cells 2022 Feb 4;11(3) doi: 10.3390/cells11030538. PMID: 35159348Free PMC Article
Long Z, Irish M, Hodges JR, Halliday G, Piguet O, Burrell JR
Neurobiol Aging 2021 Nov;107:11-20. Epub 2021 Jul 15 doi: 10.1016/j.neurobiolaging.2021.07.004. PMID: 34371283

Clinical prediction guides

Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
Donohue C, Gray LT, Anderson A, DiBiase L, Wymer JP, Plowman EK
J Speech Lang Hear Res 2023 Jan 12;66(1):154-162. Epub 2022 Dec 16 doi: 10.1044/2022_JSLHR-22-00312. PMID: 36525626Free PMC Article
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Long Z, Irish M, Hodges JR, Halliday G, Piguet O, Burrell JR
Neurobiol Aging 2021 Nov;107:11-20. Epub 2021 Jul 15 doi: 10.1016/j.neurobiolaging.2021.07.004. PMID: 34371283
Chen H, Zhang J, Wang T, Zhang S, Lai Q, Huang S, Zeng P
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4497-e4508. doi: 10.1210/clinem/dgab465. PMID: 34171091

Recent systematic reviews

Jandhyala R
BMC Med Res Methodol 2023 May 20;23(1):121. doi: 10.1186/s12874-023-01947-z. PMID: 37210484Free PMC Article
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Wadman RI, van der Pol WL, Bosboom WM, Asselman FL, van den Berg LH, Iannaccone ST, Vrancken AF
Cochrane Database Syst Rev 2020 Jan 6;1(1):CD006282. doi: 10.1002/14651858.CD006282.pub5. PMID: 32006461Free PMC Article
Long C, Amoasii L, Bassel-Duby R, Olson EN
JAMA Neurol 2016 Nov 1;73(11):1349-1355. doi: 10.1001/jamaneurol.2016.3388. PMID: 27668807Free PMC Article
Ng L, Khan F, Mathers S
Cochrane Database Syst Rev 2009 Oct 7;(4):CD007425. doi: 10.1002/14651858.CD007425.pub2. PMID: 19821416

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