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Amyotrophic lateral sclerosis type 18(ALS18)

MedGen UID:
766633
Concept ID:
C3553719
Disease or Syndrome
Synonym: PFN1-Related Amyotrophic Lateral Sclerosis
 
Gene (location): PFN1 (17p13.2)
 
Monarch Initiative: MONDO:0013891
OMIM®: 614808

Definition

Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the PFN1 gene. [from MONDO]

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
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

Smith R, Hovren H, Bowser R, Bakkar N, Garruto R, Ludolph A, Ravits J, Gaertner L, Murphy D, Lebovitz R
Eur J Neurol 2024 Apr;31(4):e16206. Epub 2024 Jan 25 doi: 10.1111/ene.16206. PMID: 38270442Free 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
Canosa A, Pagani M, Brunetti M, Barberis M, Iazzolino B, Ilardi A, Cammarosano S, Manera U, Moglia C, Calvo A, Cistaro A, Chiò A
Eur J Neurol 2019 Feb;26(2):306-312. Epub 2018 Oct 24 doi: 10.1111/ene.13812. PMID: 30240096

Curated

Orphanet, Amyotrophic lateral sclerosis, 2007

Recent clinical studies

Etiology

Baudin E, Goichot B, Berruti A, Hadoux J, Moalla S, Laboureau S, Nölting S, de la Fouchardière C, Kienitz T, Deutschbein T, Zovato S, Amar L, Haissaguerre M, Timmers H, Niccoli P, Faggiano A, Angokai M, Lamartina L, Luca F, Cosentini D, Hahner S, Beuschlein F, Attard M, Texier M, Fassnacht M; ENDOCAN-COMETE; ENSAT Networks
Lancet 2024 Mar 16;403(10431):1061-1070. Epub 2024 Feb 22 doi: 10.1016/S0140-6736(23)02554-0. PMID: 38402886
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
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Chatwin M, Simonds AK
Respir Care 2020 Feb;65(2):135-143. Epub 2019 Nov 5 doi: 10.4187/respcare.06882. PMID: 31690614

Diagnosis

Tan RH, McCann H, Shepherd CE, Pinkerton M, Mazumder S, Devenney EM, Adler GL, Rowe DB, Kril J, Halliday GM, Kiernan MC
Acta Neuropathol Commun 2023 Nov 13;11(1):180. doi: 10.1186/s40478-023-01670-2. PMID: 37957721Free PMC Article
Henden L, Fearnley LG, Grima N, McCann EP, Dobson-Stone C, Fitzpatrick L, Friend K, Hobson L, Chan Moi Fat S, Rowe DB, D'Silva S, Kwok JB, Halliday GM, Kiernan MC, Mazumder S, Timmins HC, Zoing M, Pamphlett R, Adams L, Bahlo M, Blair IP, Williams KL
Sci Adv 2023 May 5;9(18):eade2044. doi: 10.1126/sciadv.ade2044. PMID: 37146135Free PMC Article
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Chatwin M, Simonds AK
Respir Care 2020 Feb;65(2):135-143. Epub 2019 Nov 5 doi: 10.4187/respcare.06882. PMID: 31690614
Ziff OJ, Patani R
Aging Cell 2019 Feb;18(1):e12862. Epub 2018 Dec 19 doi: 10.1111/acel.12862. PMID: 30565851Free PMC Article

Therapy

Baudin E, Goichot B, Berruti A, Hadoux J, Moalla S, Laboureau S, Nölting S, de la Fouchardière C, Kienitz T, Deutschbein T, Zovato S, Amar L, Haissaguerre M, Timmers H, Niccoli P, Faggiano A, Angokai M, Lamartina L, Luca F, Cosentini D, Hahner S, Beuschlein F, Attard M, Texier M, Fassnacht M; ENDOCAN-COMETE; ENSAT Networks
Lancet 2024 Mar 16;403(10431):1061-1070. Epub 2024 Feb 22 doi: 10.1016/S0140-6736(23)02554-0. PMID: 38402886
Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, Ashizawa T, Day JW, Dent G, Tanner MK, Duong T, Greene EP, Herbelin L, Johnson NE, King W, Kissel JT, Leung DG, Lott DJ, Norris DA, Pucillo EM, Schell W, Statland JM, Stinson N, Subramony SH, Xia S, Bishop KM, Bennett CF
Lancet Neurol 2023 Mar;22(3):218-228. doi: 10.1016/S1474-4422(23)00001-7. PMID: 36804094
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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Volpe CM, Nogueira-Machado JA
Recent Pat Endocr Metab Immune Drug Discov 2015;9(1):40-5. doi: 10.2174/1872214809666150407111420. PMID: 25845840

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
Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, Ashizawa T, Day JW, Dent G, Tanner MK, Duong T, Greene EP, Herbelin L, Johnson NE, King W, Kissel JT, Leung DG, Lott DJ, Norris DA, Pucillo EM, Schell W, Statland JM, Stinson N, Subramony SH, Xia S, Bishop KM, Bennett CF
Lancet Neurol 2023 Mar;22(3):218-228. doi: 10.1016/S1474-4422(23)00001-7. PMID: 36804094
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Chatwin M, Simonds AK
Respir Care 2020 Feb;65(2):135-143. Epub 2019 Nov 5 doi: 10.4187/respcare.06882. PMID: 31690614

Clinical prediction guides

Tan RH, McCann H, Shepherd CE, Pinkerton M, Mazumder S, Devenney EM, Adler GL, Rowe DB, Kril J, Halliday GM, Kiernan MC
Acta Neuropathol Commun 2023 Nov 13;11(1):180. doi: 10.1186/s40478-023-01670-2. PMID: 37957721Free PMC Article
Huang Y, Liu B, Sinha SC, Amin S, Gan L
Mol Neurodegener 2023 Nov 8;18(1):79. doi: 10.1186/s13024-023-00672-x. PMID: 37941028Free 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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Chatwin M, Simonds AK
Respir Care 2020 Feb;65(2):135-143. Epub 2019 Nov 5 doi: 10.4187/respcare.06882. PMID: 31690614

Recent systematic reviews

Soto-Lara M, Silva-Loredo M, Monroy-Córdoba JR, Flores-Ordoñez P, Cervera-Delgadillo NG, Carrillo-Mora P
Complement Ther Med 2023 May;73:102932. Epub 2023 Feb 15 doi: 10.1016/j.ctim.2023.102932. PMID: 36805318
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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Wadman RI, van der Pol WL, Bosboom WM, Asselman FL, van den Berg LH, Iannaccone ST, Vrancken AF
Cochrane Database Syst Rev 2019 Dec 11;12(12):CD006281. doi: 10.1002/14651858.CD006281.pub5. PMID: 31825542Free PMC Article
Srinivas S, Wali AR, Pham MH
Neurosurg Focus 2019 Mar 1;46(3):E6. doi: 10.3171/2019.1.FOCUS18596. PMID: 30835675

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