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Amyotrophic lateral sclerosis 17(ALS17)

MedGen UID:
373010
Concept ID:
C1836076
Disease or Syndrome
Synonyms: ALS17; AMYOTROPHIC LATERAL SCLEROSIS, CHMP2B-RELATED
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): CHMP2B (3p11.2)
OMIM®: 614696

Disease characteristics

Excerpted from the GeneReview: Amyotrophic Lateral Sclerosis Overview
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper motor neurons (UMN) and lower motor neurons (LMN). UMN signs include hyperreflexia, extensor plantar response, increased muscle tone, and weakness in a topographic representation. LMN signs include weakness, muscle wasting, hyporeflexia, muscle cramps, and fasciculations. Initial presentation varies. Affected individuals typically present with either asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia). Other findings may include muscle fasciculations, muscle cramps, and labile affect, but not necessarily mood. Regardless of initial symptoms, atrophy and weakness eventually affect other muscles. The mean age of onset is 56 years in individuals with no known family history and 46 years in individuals with more than one affected family member (familial ALS or FALS). Average disease duration is about three years, but it can vary significantly. Death usually results from compromise of the respiratory muscles. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Definition  |  Causes  |  Evaluation Strategy  |  Genetic Counseling  |  Resources  |  Management  |  References  |  Chapter Notes
Authors:
Lisa Kinsley  |  Teepu Siddique   view full author information

Additional descriptions

From OMIM
ALS17 is an adult-onset progressive neurodegenerative disorder with predominantly lower motor neuron involvement, manifest as muscle weakness and wasting of the upper and lower limbs, bulbar signs, and respiratory insufficiency (summary by Cox et al., 2010).  http://www.omim.org/entry/614696
From GHR
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.There 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.The 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.Approximately 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.A 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.  https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis

Clinical features

Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
Amyotrophic lateral sclerosis
MedGen UID:
274
Concept ID:
C0002736
Disease or Syndrome
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper motor neurons (UMN) and lower motor neurons (LMN). UMN signs include hyperreflexia, extensor plantar response, increased muscle tone, and weakness in a topographic representation. LMN signs include weakness, muscle wasting, hyporeflexia, muscle cramps, and fasciculations. Initial presentation varies. Affected individuals typically present with either asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia). Other findings may include muscle fasciculations, muscle cramps, and labile affect, but not necessarily mood. Regardless of initial symptoms, atrophy and weakness eventually affect other muscles. The mean age of onset is 56 years in individuals with no known family history and 46 years in individuals with more than one affected family member (familial ALS or FALS). Average disease duration is about three years, but it can vary significantly. Death usually results from compromise of the respiratory muscles.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
If you have a swallowing disorder, you may have difficulty or pain when swallowing. Some people cannot swallow at all. Others may have trouble swallowing liquids, foods, or saliva. This makes it hard to eat. Often, it can be difficult to take in enough calories and fluids to nourish your body. Anyone can have a swallowing disorder, but it is more likely in the elderly. It often happens because of other conditions, including. - Nervous system disorders, such as Parkinson's disease and cerebral palsy. - Problems with your esophagus, including GERD (gastroesophageal reflux disease). - Stroke. - Head or spinal cord injury. - Cancer of the head, neck, or esophagus. Medicines can help some people, while others may need surgery. Swallowing treatment with a speech-language pathologist can help. You may find it helpful to change your diet or hold your head or neck in a certain way when you eat. In very serious cases, people may need feeding tubes. NIH: National Institute on Deafness and Other Communication Disorders.
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.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Frontotemporal dementia
MedGen UID:
83266
Concept ID:
C0338451
Disease or Syndrome
The clinical manifestations of MAPT-related disorders (MAPT-related tauopathies) are most typically those of frontotemporal dementia (FTDP-17), but also include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), mild late-onset parkinsonism, and dementia with epilepsy. Clinical presentation of frontotemporal dementia (FTD) is variable: some present with slowly progressive behavioral changes, language disturbances, and/or extrapyramidal signs, whereas others present with rigidity, bradykinesia, supranuclear palsy, and saccadic eye movement disorders. Onset is usually between ages 40 and 60 years, but may be earlier or later. The disease progresses over a few years into profound dementia with mutism. PSP is characterized by progressive vertical gaze palsy in combination with a prominent loss of balance at early stages of the disease. With progression, axial rigidity, dysarthria, and dysphagia become prominent, often in combination with a frontal dysexecutive syndrome. CBD is a progressive neurodegenerative disorder which affects both the frontoparietal cortex and the basal ganglia, resulting in a mild to moderate dementia in combination with asymmetric parkinsonism, ideomotor apraxia, aphasia, and an alien-hand syndrome.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Sign or Symptom
Reduction of neurologic reflexes such as the knee-jerk reaction.
Bulbar signs
MedGen UID:
347246
Concept ID:
C1856507
Finding
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Skeletal muscle atrophy
MedGen UID:
902598
Concept ID:
C0234958
Disease or Syndrome
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding

Recent clinical studies

Etiology

Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Halliday GM, Kiernan MC, Kril JJ, Mito R, Masuda-Suzukake M, Hasegawa M, McCann H, Bartley L, Dobson-Stone C, Kwok JB, Hornberger M, Hodges JR, Tan RH
J Neurol Sci 2016 Jul 15;366:197-201. Epub 2016 May 4 doi: 10.1016/j.jns.2016.05.005. PMID: 27288806
Moura MC, Casulari LA, Carvalho Garbi Novaes MR
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):275-81. Epub 2016 Feb 5 doi: 10.3109/21678421.2016.1140210. PMID: 26850047
Devine MS, Ballard E, O'Rourke P, Kiernan MC, Mccombe PA, Henderson RD
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):184-90. Epub 2015 Dec 24 doi: 10.3109/21678421.2015.1125502. PMID: 26700804
Sanjuán-López P, Valiño-López P, Ricoy-Gabaldón J, Verea-Hernando H
Arch Bronconeumol 2014 Dec;50(12):509-13. Epub 2014 Jun 12 doi: 10.1016/j.arbres.2014.04.010. PMID: 24931271

Diagnosis

Schuster C, Hardiman O, Bede P
BMC Neurol 2017 Apr 17;17(1):73. doi: 10.1186/s12883-017-0854-x. PMID: 28412941Free PMC Article
Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Blasco H, Patin F, Andres CR, Corcia P, Gordon PH
Expert Opin Pharmacother 2016 Aug;17(12):1669-82. Epub 2016 Jul 4 doi: 10.1080/14656566.2016.1202919. PMID: 27356036
Halliday GM, Kiernan MC, Kril JJ, Mito R, Masuda-Suzukake M, Hasegawa M, McCann H, Bartley L, Dobson-Stone C, Kwok JB, Hornberger M, Hodges JR, Tan RH
J Neurol Sci 2016 Jul 15;366:197-201. Epub 2016 May 4 doi: 10.1016/j.jns.2016.05.005. PMID: 27288806
Sanjuán-López P, Valiño-López P, Ricoy-Gabaldón J, Verea-Hernando H
Arch Bronconeumol 2014 Dec;50(12):509-13. Epub 2014 Jun 12 doi: 10.1016/j.arbres.2014.04.010. PMID: 24931271

Therapy

Schuster C, Hardiman O, Bede P
BMC Neurol 2017 Apr 17;17(1):73. doi: 10.1186/s12883-017-0854-x. PMID: 28412941Free PMC Article
Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Blasco H, Patin F, Andres CR, Corcia P, Gordon PH
Expert Opin Pharmacother 2016 Aug;17(12):1669-82. Epub 2016 Jul 4 doi: 10.1080/14656566.2016.1202919. PMID: 27356036
Tokuda E, Furukawa Y
Int J Mol Sci 2016 Apr 28;17(5) doi: 10.3390/ijms17050636. PMID: 27136532Free PMC Article
Bacci ED, Staniewska D, Coyne KS, Boyer S, White LA, Zach N, Cedarbaum JM; Pooled Resource Open-Access ALS Clinical Trials Consortium.
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):157-67. Epub 2015 Oct 16 doi: 10.3109/21678421.2015.1095930. PMID: 26473473

Prognosis

Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Benstead T, Jackson-Tarlton C, Leddin D
Can J Neurol Sci 2016 Nov;43(6):796-800. Epub 2016 Apr 4 doi: 10.1017/cjn.2016.28. PMID: 27039940
Moura MC, Casulari LA, Carvalho Garbi Novaes MR
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):275-81. Epub 2016 Feb 5 doi: 10.3109/21678421.2016.1140210. PMID: 26850047
Goursaud S, Schäfer S, Dumont AO, Vergouts M, Gallo A, Desmet N, Deumens R, Hermans E
Exp Neurol 2015 Jan;263:91-101. Epub 2014 Oct 13 doi: 10.1016/j.expneurol.2014.09.022. PMID: 25311268
Sanjuán-López P, Valiño-López P, Ricoy-Gabaldón J, Verea-Hernando H
Arch Bronconeumol 2014 Dec;50(12):509-13. Epub 2014 Jun 12 doi: 10.1016/j.arbres.2014.04.010. PMID: 24931271

Clinical prediction guides

Schuster C, Hardiman O, Bede P
BMC Neurol 2017 Apr 17;17(1):73. doi: 10.1186/s12883-017-0854-x. PMID: 28412941Free PMC Article
Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Sandstedt P, Johansson S, Ytterberg C, Ingre C, Holmqvist LW, Kierkegaard M
J Neurol Sci 2016 Nov 15;370:269-273. Epub 2016 Sep 21 doi: 10.1016/j.jns.2016.09.034. PMID: 27772773
Devine MS, Ballard E, O'Rourke P, Kiernan MC, Mccombe PA, Henderson RD
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):184-90. Epub 2015 Dec 24 doi: 10.3109/21678421.2015.1125502. PMID: 26700804
Goursaud S, Schäfer S, Dumont AO, Vergouts M, Gallo A, Desmet N, Deumens R, Hermans E
Exp Neurol 2015 Jan;263:91-101. Epub 2014 Oct 13 doi: 10.1016/j.expneurol.2014.09.022. PMID: 25311268

Recent systematic reviews

Ferreira GD, Costa AC, Plentz RD, Coronel CC, Sbruzzi G
Physiotherapy 2016 Sep;102(3):221-8. Epub 2016 Mar 26 doi: 10.1016/j.physio.2016.01.002. PMID: 27026167
Prado Lde G, Bicalho IC, Vidigal-Lopes M, Ferreira CJ, Mageste Barbosa LS, Gomez RS, De Souza LC, Teixeira AL
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):282-8. Epub 2016 Feb 8 doi: 10.3109/21678421.2016.1143011. PMID: 26854959
Lysogorskaia EV, Abramycheva NY, Zakharova MN, Stepanova MS, Moroz AA, Rossokhin AV, Illarioshkin SN
Amyotroph Lateral Scler Frontotemporal Degener 2015;17(1-2):135-41. Epub 2015 Nov 9 doi: 10.3109/21678421.2015.1107100. PMID: 26551617
Fogh I, Ratti A, Gellera C, Lin K, Tiloca C, Moskvina V, Corrado L, Sorarù G, Cereda C, Corti S, Gentilini D, Calini D, Castellotti B, Mazzini L, Querin G, Gagliardi S, Del Bo R, Conforti FL, Siciliano G, Inghilleri M, Saccà F, Bongioanni P, Penco S, Corbo M, Sorbi S, Filosto M, Ferlini A, Di Blasio AM, Signorini S, Shatunov A, Jones A, Shaw PJ, Morrison KE, Farmer AE, Van Damme P, Robberecht W, Chiò A, Traynor BJ, Sendtner M, Melki J, Meininger V, Hardiman O, Andersen PM, Leigh NP, Glass JD, Overste D, Diekstra FP, Veldink JH, van Es MA, Shaw CE, Weale ME, Lewis CM, Williams J, Brown RH, Landers JE, Ticozzi N, Ceroni M, Pegoraro E, Comi GP, D'Alfonso S, van den Berg LH, Taroni F, Al-Chalabi A, Powell J, Silani V; SLAGEN Consortium and Collaborators.
Hum Mol Genet 2014 Apr 15;23(8):2220-31. Epub 2013 Nov 20 doi: 10.1093/hmg/ddt587. PMID: 24256812Free PMC Article
Pfister T, Sekhon R, White M, Scott P, Munro S, Johnston M, Kalra S, Korngut L
Amyotroph Lateral Scler Frontotemporal Degener 2013 May;14(4):273-7. Epub 2013 Jan 4 doi: 10.3109/21678421.2012.754044. PMID: 23286750

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