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Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia(ALS15)

MedGen UID:
477090
Concept ID:
C3275459
Disease or Syndrome
Synonyms: ALS15; AMYOTROPHIC LATERAL SCLEROSIS 15 WITH FRONTOTEMPORAL DEMENTIA; UBQLN2-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
 
Gene (location): UBQLN2 (Xp11.21)
OMIM®: 300857

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 description

From GHR
Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that are important for controlling muscle movement and strength. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die over time, leading to problems with muscle control and 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 the condition. 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 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 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 wastes away (atrophies). Individuals with ALS lose their strength and the ability to walk. Affected individuals eventually become wheelchair-dependent. 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 a condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. People with FTD increasingly require help with personal care and other activities of daily living. 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.  http://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis

Clinical features

Dysarthria
MedGen UID:
333395
Concept ID:
C1839743
Finding
Dysphagia
MedGen UID:
342867
Concept ID:
C1853381
Finding
Dystonia
MedGen UID:
504804
Concept ID:
CN001220
Finding
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Frontotemporal dementia
MedGen UID:
505124
Concept ID:
CN001944
Finding
A dementia associated with degeneration of the frontotemporal lobe and clinically associated with personality and behavioral changes such as disinhibition, apathy, and lack of insight. The hallmark feature of frontotemporal dementia is the presentation with focal syndromes such as progressive language dysfunction, or aphasia, or behavioral changes characteristic of frontal lobe disorders.
Athetosis
MedGen UID:
505190
Concept ID:
CN002093
Finding
Athetosis (from the Greek word for 'changeable' or 'unfixed') refers to an inability to sustain the muscles of the fingers, toes, tongue, or any other group of muscles in a fixed position. Instead, posture is interrupted by slow, purposeless involuntary movements.
Amyotrophic lateral sclerosis
MedGen UID:
506059
Concept ID:
CN006437
Finding
Dysphagia
MedGen UID:
342867
Concept ID:
C1853381
Finding

Recent clinical studies

Etiology

Machts J, Bittner V, Kasper E, Schuster C, Prudlo J, Abdulla S, Kollewe K, Petri S, Dengler R, Heinze HJ, Vielhaber S, Schoenfeld MA, Bittner DM
BMC Neurosci 2014 Jun 30;15:83. doi: 10.1186/1471-2202-15-83. [Epub ahead of print] PMID: 24981872Free PMC Article
Tremolizzo L, Susani E, Aliprandi A, Salmaggi A, Ferrarese C, Appollonio I
Amyotroph Lateral Scler Frontotemporal Degener 2014 Dec;15(7-8):546-50. Epub 2014 May 27 doi: 10.3109/21678421.2014.913636. [Epub ahead of print] PMID: 24863345
Savage SA, Lillo P, Kumfor F, Kiernan MC, Piguet O, Hodges JR
Amyotroph Lateral Scler Frontotemporal Degener 2014 Mar;15(1-2):39-46. Epub 2013 Jul 29 doi: 10.3109/21678421.2013.809763. [Epub ahead of print] PMID: 23889548
Burrell JR, Carpenter RH, Hodges JR, Kiernan MC
Amyotroph Lateral Scler Frontotemporal Degener 2013 May;14(4):294-301. Epub 2013 Apr 16 doi: 10.3109/21678421.2013.783077. [Epub ahead of print] PMID: 23586894
Lillo P, Mioshi E, Burrell JR, Kiernan MC, Hodges JR, Hornberger M
PLoS One 2012;7(8):e43993. Epub 2012 Aug 29 doi: 10.1371/journal.pone.0043993. PMID: 22952843Free PMC Article

Diagnosis

Ambikairajah A, Devenney E, Flanagan E, Yew B, Mioshi E, Kiernan MC, Hodges JR, Hornberger M
Amyotroph Lateral Scler Frontotemporal Degener 2014 Jun;15(3-4):226-34. Epub 2014 Feb 18 doi: 10.3109/21678421.2014.880180. [Epub ahead of print] PMID: 24533506
Savage SA, Lillo P, Kumfor F, Kiernan MC, Piguet O, Hodges JR
Amyotroph Lateral Scler Frontotemporal Degener 2014 Mar;15(1-2):39-46. Epub 2013 Jul 29 doi: 10.3109/21678421.2013.809763. [Epub ahead of print] PMID: 23889548
Lillo P, Mioshi E, Burrell JR, Kiernan MC, Hodges JR, Hornberger M
PLoS One 2012;7(8):e43993. Epub 2012 Aug 29 doi: 10.1371/journal.pone.0043993. PMID: 22952843Free PMC Article
Sha SJ, Takada LT, Rankin KP, Yokoyama JS, Rutherford NJ, Fong JC, Khan B, Karydas A, Baker MC, DeJesus-Hernandez M, Pribadi M, Coppola G, Geschwind DH, Rademakers R, Lee SE, Seeley W, Miller BL, Boxer AL
Neurology 2012 Sep 4;79(10):1002-11. Epub 2012 Aug 8 doi: 10.1212/WNL.0b013e318268452e. [Epub ahead of print] PMID: 22875087Free PMC Article
Hsiung GY, DeJesus-Hernandez M, Feldman HH, Sengdy P, Bouchard-Kerr P, Dwosh E, Butler R, Leung B, Fok A, Rutherford NJ, Baker M, Rademakers R, Mackenzie IR
Brain 2012 Mar;135(Pt 3):709-22. Epub 2012 Feb 17 doi: 10.1093/brain/awr354. [Epub ahead of print] PMID: 22344582Free PMC Article

Therapy

Shatunov A, Mok K, Newhouse S, Weale ME, Smith B, Vance C, Johnson L, Veldink JH, van Es MA, van den Berg LH, Robberecht W, Van Damme P, Hardiman O, Farmer AE, Lewis CM, Butler AW, Abel O, Andersen PM, Fogh I, Silani V, Chiò A, Traynor BJ, Melki J, Meininger V, Landers JE, McGuffin P, Glass JD, Pall H, Leigh PN, Hardy J, Brown RH Jr, Powell JF, Orrell RW, Morrison KE, Shaw PJ, Shaw CE, Al-Chalabi A
Lancet Neurol 2010 Oct;9(10):986-94. doi: 10.1016/S1474-4422(10)70197-6. PMID: 20801717Free PMC Article
Matsumoto S, Kusaka H, Ito H, Shibata N, Asayama T, Imai T
Clin Neuropathol 1996 Jan-Feb;15(1):41-6. PMID: 8998856

Prognosis

Tremolizzo L, Susani E, Aliprandi A, Salmaggi A, Ferrarese C, Appollonio I
Amyotroph Lateral Scler Frontotemporal Degener 2014 Dec;15(7-8):546-50. Epub 2014 May 27 doi: 10.3109/21678421.2014.913636. [Epub ahead of print] PMID: 24863345
Cavallo M, Adenzato M, Macpherson SE, Karwig G, Enrici I, Abrahams S
PLoS One 2011;6(10):e25948. Epub 2011 Oct 5 doi: 10.1371/journal.pone.0025948. PMID: 21998727Free PMC Article
Heidler-Gary J, Hillis AE
Amyotroph Lateral Scler 2007 Oct;8(5):276-82. doi: 10.1080/17482960701381911. PMID: 17917849
Tsuchiya K, Ikeda K, Haga C, Kobayashi T, Morimatsu Y, Nakano I, Matsushita M
Acta Neuropathol 2001 Jun;101(6):625-30. PMID: 11515792
Matsumoto S, Kusaka H, Ito H, Shibata N, Asayama T, Imai T
Clin Neuropathol 1996 Jan-Feb;15(1):41-6. PMID: 8998856

Clinical prediction guides

Machts J, Bittner V, Kasper E, Schuster C, Prudlo J, Abdulla S, Kollewe K, Petri S, Dengler R, Heinze HJ, Vielhaber S, Schoenfeld MA, Bittner DM
BMC Neurosci 2014 Jun 30;15:83. doi: 10.1186/1471-2202-15-83. [Epub ahead of print] PMID: 24981872Free PMC Article
Tremolizzo L, Susani E, Aliprandi A, Salmaggi A, Ferrarese C, Appollonio I
Amyotroph Lateral Scler Frontotemporal Degener 2014 Dec;15(7-8):546-50. Epub 2014 May 27 doi: 10.3109/21678421.2014.913636. [Epub ahead of print] PMID: 24863345
Ambikairajah A, Devenney E, Flanagan E, Yew B, Mioshi E, Kiernan MC, Hodges JR, Hornberger M
Amyotroph Lateral Scler Frontotemporal Degener 2014 Jun;15(3-4):226-34. Epub 2014 Feb 18 doi: 10.3109/21678421.2014.880180. [Epub ahead of print] PMID: 24533506
Cavallo M, Adenzato M, Macpherson SE, Karwig G, Enrici I, Abrahams S
PLoS One 2011;6(10):e25948. Epub 2011 Oct 5 doi: 10.1371/journal.pone.0025948. PMID: 21998727Free PMC Article
Heidler-Gary J, Hillis AE
Amyotroph Lateral Scler 2007 Oct;8(5):276-82. doi: 10.1080/17482960701381911. PMID: 17917849

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