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Frontotemporal dementia(FTD)

MedGen UID:
83266
Concept ID:
C0338451
Disease or Syndrome
Synonyms: Dementia, frontotemporal, with or without parkinsonism; Dementia, frontotemporal, with parkinsonism; frontotemporal dementia with parkinsonism-17; FRONTOTEMPORAL LOBAR DEGENERATION WITH TAU INCLUSIONS; FRONTOTEMPORAL LOBE DEMENTIA; Frontotemporal lobe dementia (FLDEM); FTD; FTLD WITH TAU INCLUSIONS; Multiple system tauopathy with presenile dementia; WILHELMSEN-LYNCH DISEASE
SNOMED CT: Frontotemporal dementia (230270009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): MAPT (17q21.31); PSEN1 (14q24.2)
 
HPO: HP:0002145
Monarch Initiative: MONDO:0017276
OMIM®: 600274
Orphanet: ORPHA282

Definition

Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below). Clinical Variability of Tauopathies Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy. Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104), Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Frontotemporal Lobar Degeneration Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLALS7 (600795), caused by mutation in the CHMP2B gene (609512) on chromosome 3p11; inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS1 (105550), caused by mutation in the C9ORF72 gene (614260) on 9p21. In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822). [from OMIM]

Additional description

From MedlinePlus Genetics
Frontotemporal dementia with parkinsonism-17 (FTDP-17) is a brain disorder. It is part of a group of conditions, called frontotemporal dementia or frontotemporal degeneration, that are characterized by a loss of nerve cells (neurons) in areas of the brain called the frontal and temporal lobes. Over time, a loss of these cells can affect personality, behavior, language, and movement.

The signs and symptoms of FTDP-17 usually become noticeable in a person's forties or fifties. Most affected people survive 5 to 10 years after the appearance of symptoms, although a few have survived for two decades or more.

Changes in personality and behavior are often early signs of FTDP-17. These changes include a loss of inhibition, inappropriate emotional responses, restlessness, neglect of personal hygiene, and a general loss of interest in activities and events. The disease also leads to deterioration of cognitive functions (dementia), including problems with judgment, planning, and concentration. Some people with FTDP-17 develop psychiatric symptoms, including obsessive-compulsive behaviors, strongly held false beliefs (delusions), and false perceptions (hallucinations). It may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.

Many people with FTDP-17 develop problems with speech and language. They may have trouble finding words, confuse one word with another (semantic paraphasias), and repeat words spoken by others (echolalia). Difficulties with speech and language worsen over time, and most affected individuals eventually lose the ability to communicate.

FTDP-17 is also characterized by problems with movement that worsen over time. Many affected individuals develop features of parkinsonism, including tremors, rigidity, and unusually slow movement (bradykinesia). As the disease progresses, most affected individuals become unable to walk. Some people with FTDP-17 also have restricted up-and-down eye movement (vertical gaze palsy) and rapid abnormal movements of both eyes (saccades).  https://medlineplus.gov/genetics/condition/frontotemporal-dementia-with-parkinsonism-17

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.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Language disorder
MedGen UID:
44069
Concept ID:
C0023015
Mental or Behavioral Dysfunction
Language impairment is a deficit in comprehension or production of language that includes reduced vocabulary, limited sentence structure, or impairments in written or spoken communication. Language abilities are substantially and quantifiably below age expectations.
Apathy
MedGen UID:
39083
Concept ID:
C0085632
Mental or Behavioral Dysfunction
Apathy is a quantitative reduction of motivation and the initiation and persistence of goal-directed behavior, where the accompanying emotions, thoughts, and social interactions are also suppressed.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Parkinsonism
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Frontotemporal dementia
MedGen UID:
83266
Concept ID:
C0338451
Disease or Syndrome
Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below). Clinical Variability of Tauopathies Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy. Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104), Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Frontotemporal Lobar Degeneration Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLALS7 (600795), caused by mutation in the CHMP2B gene (609512) on chromosome 3p11; inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS1 (105550), caused by mutation in the C9ORF72 gene (614260) on 9p21. In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822).
Frontal lobe dementia
MedGen UID:
572577
Concept ID:
C0338455
Disease or Syndrome
Inappropriate laughter
MedGen UID:
98407
Concept ID:
C0424304
Finding
Laughing that may be excessive and/or inappropriate in context (e.g., laughing at a funeral while others are crying).
Diminished motivation
MedGen UID:
96830
Concept ID:
C0456814
Finding
A reduction in goal-directed behavior, that is, motivation, is the determinant of behavior and adaptation that allows individuals to get started, be energized to perform a sustained and directed action.
Disinhibition
MedGen UID:
633911
Concept ID:
C0474398
Finding
Reduced ability to control, or a failure to resist a temptation, urge, or impulse. Examples include disregard for social conventions, general impulsivity, and poor risk assessment.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Primitive reflex
MedGen UID:
333065
Concept ID:
C1838319
Finding
The primitive reflexes are a group of behavioural motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
Hyperorality
MedGen UID:
325386
Concept ID:
C1838320
Finding
Hyperorality is a condition characterized by an excessive preoccupation with oral sensations and behaviors, such as chewing, sucking, biting, swallowing, and excessive mouthing of objects.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFrontotemporal dementia
Follow this link to review classifications for Frontotemporal dementia in Orphanet.

Conditions with this feature

Pick disease
MedGen UID:
116020
Concept ID:
C0236642
Disease or Syndrome
Pick disease refers to the neuropathologic finding of 'Pick bodies,' which are argyrophilic, intraneuronal inclusions, and 'Pick cells,' which are enlarged neurons. The clinical correlates of Pick disease of brain include those of frontotemporal dementia, which encompass the behavioral variant of FTD, semantic dementia, and progressive nonfluent aphasia (summary by Piguet et al., 2011). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), progressive supranuclear palsy (601104), and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease,' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies.
Frontotemporal dementia
MedGen UID:
83266
Concept ID:
C0338451
Disease or Syndrome
Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below). Clinical Variability of Tauopathies Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy. Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104), Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Frontotemporal Lobar Degeneration Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLALS7 (600795), caused by mutation in the CHMP2B gene (609512) on chromosome 3p11; inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS1 (105550), caused by mutation in the C9ORF72 gene (614260) on 9p21. In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822).
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7
MedGen UID:
318833
Concept ID:
C1833296
Disease or Syndrome
CHMP2B frontotemporal dementia (CHMP2B-FTD) has been described in a single family from Denmark, in one individual with familial FTD from Belgium, and in one individual with FTD and no family history. It typically starts between ages 46 and 65 years with subtle personality changes and slowly progressive behavioral changes, dysexecutive syndrome, dyscalculia, and language disturbances. Disinhibition or loss of initiative is the most common presenting symptom. The disease progresses over a few years into profound dementia with extrapyramidal symptoms and mutism. Several individuals have developed an asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs that may be related to treatment with neuroleptic drugs. Symptoms and disease course are highly variable. Disease duration may be as short as three years or longer than 20 years.
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
MedGen UID:
375285
Concept ID:
C1843792
Disease or Syndrome
The spectrum of GRN frontotemporal dementia (GRN-FTD) includes the behavioral variant (bvFTD), primary progressive aphasia (PPA; further subcategorized as progressive nonfluent aphasia [PNFA] and semantic dementia [SD]), and movement disorders with extrapyramidal features such as parkinsonism and corticobasal syndrome (CBS). A broad range of clinical features both within and between families is observed. The age of onset ranges from 35 to 87 years. Behavioral disturbances are the most common early feature, followed by progressive aphasia. Impairment in executive function manifests as loss of judgment and insight. In early stages, PPA often manifests as deficits in naming, word finding, or word comprehension. In late stages, affected individuals often become mute and lose their ability to communicate. Early findings of parkinsonism include rigidity, bradykinesia or akinesia (slowing or absence of movements), limb dystonia, apraxia (loss of ability to carry out learned purposeful movements), and disequilibrium. Late motor findings may include myoclonus, dysarthria, and dysphagia. Most affected individuals eventually lose the ability to walk. Disease duration is three to 12 years.
Perry syndrome
MedGen UID:
357007
Concept ID:
C1868594
Disease or Syndrome
The spectrum of DCTN1-related neurodegeneration includes Perry syndrome, distal hereditary motor neuronopathy type 7B (dHMN7B), frontotemporal dementia (FTD), motor neuron disease / amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy. Some individuals present with overlapping phenotypes (e.g., FTD-ALS, Perry syndrome-dHMN7B). Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. The mean age of onset in those with Perry syndrome is 49 years (range: 35-70 years), and the mean disease duration is five years (range: 2-14 years). In most affected persons, the reported cause/circumstance of death relates to sudden death/hypoventilation or suicide.
Amyotrophic lateral sclerosis type 10
MedGen UID:
383137
Concept ID:
C2677565
Disease or Syndrome
A neurodegenerative disease with characteristics of progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. There is evidence this disease is caused by heterozygous mutation in the TARDBP gene that encodes the TDP43 protein on chromosome 1p36.
Autosomal recessive Parkinson disease 14
MedGen UID:
414488
Concept ID:
C2751842
Disease or Syndrome
Generally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease.\n\nParkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.\n\nOften the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.\n\nParkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.
Amyotrophic lateral sclerosis type 15
MedGen UID:
477090
Concept ID:
C3275459
Disease or Syndrome
Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the UBQLN2 gene.
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2
MedGen UID:
815798
Concept ID:
C3809468
Disease or Syndrome
Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
MedGen UID:
854771
Concept ID:
C3888102
Disease or Syndrome
C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis (C9orf72-FTD/ALS) is characterized most often by frontotemporal dementia (FTD) and upper and lower motor neuron disease (MND); however, atypical presentations also occur. Age at onset is usually between 50 and 64 years (range: 20-91 years) irrespective of the presenting manifestations, which may be pure FTD, pure amyotrophic lateral sclerosis (ALS), or a combination of the two phenotypes. The clinical presentation is highly heterogeneous and may differ between and within families, causing an unpredictable pattern and age of onset of clinical manifestations. The presence of MND correlates with an earlier age of onset and a worse overall prognosis.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 2
MedGen UID:
863085
Concept ID:
C4014648
Disease or Syndrome
CHCHD10-related disorders are characterized by a spectrum of adult-onset neurologic phenotypes that can include: Mitochondrial myopathy (may also be early onset): weakness, amyotrophy, exercise intolerance. Amyotrophic lateral sclerosis (ALS): progressive degeneration of upper motor neurons and lower motor neurons. Frontotemporal dementia (FTD): slowly progressive behavioral changes, language disturbances, cognitive decline, extrapyramidal signs. Late-onset spinal motor neuronopathy (SMA, Jokela type): weakness, cramps, and/or fasciculations; areflexia. Axonal Charcot-Marie-Tooth neuropathy: slowly progressive lower-leg muscle weakness and atrophy, small hand muscle weakness, loss of tendon reflexes, sensory abnormalities. Cerebellar ataxia: gait ataxia, kinetic ataxia (progressive loss of coordination of lower- and upper-limb movements), dysarthria/dysphagia, nystagmus, cerebellar oculomotor disorder. Because of the recent discovery of CHCHD10-related disorders and the limited number of affected individuals reported to date, the natural history of these disorders (except for SMAJ caused by the p.Gly66Val pathogenic variant) is largely unknown.
Amyotrophic lateral sclerosis type 22
MedGen UID:
863949
Concept ID:
C4015512
Disease or Syndrome
Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the TUBA4A gene.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4
MedGen UID:
902979
Concept ID:
C4225325
Disease or Syndrome
Frontotemporal dementia and/or amyotrophic lateral sclerosis-4 is an autosomal dominant neurodegenerative disorder characterized by adult or late adult onset of cognitive impairment, behavioral abnormalities, and speech apraxia and/or upper and lower motor neuron signs. The phenotype is highly variable (summary by Freischmidt et al., 2015). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550).
Frontotemporal dementia and/or amyotrophic lateral sclerosis 3
MedGen UID:
897127
Concept ID:
C4225326
Disease or Syndrome
Frontotemporal dementia and/or amyotrophic lateral sclerosis-3 is an autosomal dominant neurodegenerative disorder characterized by adult or late adult onset of cognitive impairment, behavioral abnormalities, and speech apraxia and/or upper and lower motor neuron signs. Some patients may also develop Paget disease of bone. The phenotype is highly variable, even within families (summary by Rea et al., 2014). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550).
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1
MedGen UID:
1641069
Concept ID:
C4551951
Disease or Syndrome
Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 8
MedGen UID:
1728824
Concept ID:
C5436881
Disease or Syndrome
Frontotemporal dementia and/or amyotrophic lateral sclerosis-8 (FTDALS8) is an autosomal dominant neurodegenerative disorder characterized by adult-onset dementia manifest as memory impairment, executive dysfunction, and behavioral or personality changes. Some patients may develop ALS or parkinsonism. Neuropathologic studies show frontotemporal lobar degeneration (FTLD) with tau (MAPT; 157140)- and TDP43 (605078)-immunoreactive inclusions (summary by Dobson-Stone et al., 2020). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550).
Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia
MedGen UID:
1771903
Concept ID:
C5436882
Disease or Syndrome
Amyotrophic lateral sclerosis-26 with or without frontotemporal dementia (ALS26) is an autosomal dominant neurodegenerative disorder characterized by adult onset of upper and low motor neuron disease causing bulbar dysfunction and limb weakness (ALS). Patients may also develop frontotemporal dementia (FTD) manifest as primary progressive aphasia, memory impairment, executive dysfunction, and behavioral or personality changes. Although patients may present with 1 or the other diseases, all eventually develop ALS. Neuropathologic studies of the brain and spinal cord show TDP43 (605078)-immunoreactive cytoplasmic inclusions that correlate with clinical features and Lewy body-like cytoplasmic inclusions in lower motor neurons (summary by Mackenzie et al., 2017). For a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400).
Frontotemporal dementia and/or amyotrophic lateral sclerosis 5
MedGen UID:
1756201
Concept ID:
C5436884
Disease or Syndrome
Frontotemporal dementia and/or amyotrophic lateral sclerosis-5 (FTDALS5) is an autosomal dominant neurodegenerative disorder characterized by onset of ALS or FTD symptoms in adulthood. The disease is progressive, and some patients may develop both diseases, although ALS seems to be more prevalent than FTD. The disorder usually results in premature death (summary by Williams et al., 2016). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550).

Professional guidelines

PubMed

Pérez Palmer N, Trejo Ortega B, Joshi P
Psychiatr Clin North Am 2022 Dec;45(4):639-661. Epub 2022 Oct 14 doi: 10.1016/j.psc.2022.07.010. PMID: 36396270
Volkmer A, Rogalski E, Henry M, Taylor-Rubin C, Ruggero L, Khayum R, Kindell J, Gorno-Tempini ML, Warren JD, Rohrer JD
Pract Neurol 2020 Apr;20(2):154-161. Epub 2019 Jul 29 doi: 10.1136/practneurol-2018-001921. PMID: 31358572Free PMC Article
Levin J, Kurz A, Arzberger T, Giese A, Höglinger GU
Dtsch Arztebl Int 2016 Feb 5;113(5):61-9. doi: 10.3238/arztebl.2016.0061. PMID: 26900156Free PMC Article

Curated

UK NICE Clinical guideline (CG148), Urinary incontinence in neurological disease: assessment and management, 2023

Recent clinical studies

Etiology

Boeve BF, Boxer AL, Kumfor F, Pijnenburg Y, Rohrer JD
Lancet Neurol 2022 Mar;21(3):258-272. doi: 10.1016/S1474-4422(21)00341-0. PMID: 35182511
Rhinn H, Tatton N, McCaughey S, Kurnellas M, Rosenthal A
Trends Pharmacol Sci 2022 Aug;43(8):641-652. Epub 2022 Jan 15 doi: 10.1016/j.tips.2021.11.015. PMID: 35039149
Puppala GK, Gorthi SP, Chandran V, Gundabolu G
Neurol India 2021 Sep-Oct;69(5):1144-1152. doi: 10.4103/0028-3886.329593. PMID: 34747778
Sivasathiaseelan H, Marshall CR, Agustus JL, Benhamou E, Bond RL, van Leeuwen JEP, Hardy CJD, Rohrer JD, Warren JD
Semin Neurol 2019 Apr;39(2):251-263. Epub 2019 Mar 29 doi: 10.1055/s-0039-1683379. PMID: 30925617
Bang J, Spina S, Miller BL
Lancet 2015 Oct 24;386(10004):1672-82. doi: 10.1016/S0140-6736(15)00461-4. PMID: 26595641Free PMC Article

Diagnosis

Boeve BF, Boxer AL, Kumfor F, Pijnenburg Y, Rohrer JD
Lancet Neurol 2022 Mar;21(3):258-272. doi: 10.1016/S1474-4422(21)00341-0. PMID: 35182511
Puppala GK, Gorthi SP, Chandran V, Gundabolu G
Neurol India 2021 Sep-Oct;69(5):1144-1152. doi: 10.4103/0028-3886.329593. PMID: 34747778
Olney NT, Spina S, Miller BL
Neurol Clin 2017 May;35(2):339-374. doi: 10.1016/j.ncl.2017.01.008. PMID: 28410663Free PMC Article
Bang J, Spina S, Miller BL
Lancet 2015 Oct 24;386(10004):1672-82. doi: 10.1016/S0140-6736(15)00461-4. PMID: 26595641Free PMC Article
Bott NT, Radke A, Stephens ML, Kramer JH
Neurodegener Dis Manag 2014;4(6):439-54. doi: 10.2217/nmt.14.34. PMID: 25531687Free PMC Article

Therapy

Goutman SA, Hardiman O, Al-Chalabi A, Chió A, Savelieff MG, Kiernan MC, Feldman EL
Lancet Neurol 2022 May;21(5):480-493. Epub 2022 Mar 22 doi: 10.1016/S1474-4422(21)00465-8. PMID: 35334233Free PMC Article
Azhar L, Kusumo RW, Marotta G, Lanctôt KL, Herrmann N
CNS Drugs 2022 Feb;36(2):143-165. Epub 2022 Jan 10 doi: 10.1007/s40263-021-00883-0. PMID: 35006557
Saeger HN, Olson DE
J Neurochem 2022 Jul;162(1):109-127. Epub 2021 Dec 5 doi: 10.1111/jnc.15544. PMID: 34816433Free PMC Article
Perugi G, Vannucchi G, Bedani F, Favaretto E
Curr Psychiatry Rep 2017 Jan;19(1):7. doi: 10.1007/s11920-017-0758-x. PMID: 28144880
Baird A, Samson S
Prog Brain Res 2015;217:207-35. Epub 2015 Jan 31 doi: 10.1016/bs.pbr.2014.11.028. PMID: 25725917

Prognosis

Boeve BF
Continuum (Minneap Minn) 2022 Jun 1;28(3):702-725. doi: 10.1212/CON.0000000000001105. PMID: 35678399Free PMC Article
Sivasathiaseelan H, Marshall CR, Agustus JL, Benhamou E, Bond RL, van Leeuwen JEP, Hardy CJD, Rohrer JD, Warren JD
Semin Neurol 2019 Apr;39(2):251-263. Epub 2019 Mar 29 doi: 10.1055/s-0039-1683379. PMID: 30925617
McCauley ME, Baloh RH
Acta Neuropathol 2019 May;137(5):715-730. Epub 2018 Nov 21 doi: 10.1007/s00401-018-1933-9. PMID: 30465257Free PMC Article
van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, van den Berg LH
Lancet 2017 Nov 4;390(10107):2084-2098. Epub 2017 May 25 doi: 10.1016/S0140-6736(17)31287-4. PMID: 28552366
Bott NT, Radke A, Stephens ML, Kramer JH
Neurodegener Dis Manag 2014;4(6):439-54. doi: 10.2217/nmt.14.34. PMID: 25531687Free PMC Article

Clinical prediction guides

Benussi A, Ashton NJ, Karikari TK, Alberici A, Saraceno C, Ghidoni R, Benussi L, Zetterberg H, Blennow K, Borroni B
Alzheimers Res Ther 2021 Nov 15;13(1):188. doi: 10.1186/s13195-021-00932-2. PMID: 34782010Free PMC Article
Onyike CU, Shinagawa S, Ellajosyula R
Adv Exp Med Biol 2021;1281:141-150. doi: 10.1007/978-3-030-51140-1_10. PMID: 33433874
Kawano Y, Terada S, Takenoshita S, Hayashi S, Oshima Y, Miki T, Yokota O, Yamada N
Psychogeriatrics 2020 Mar;20(2):189-195. Epub 2019 Nov 7 doi: 10.1111/psyg.12487. PMID: 31698515
Bott NT, Radke A, Stephens ML, Kramer JH
Neurodegener Dis Manag 2014;4(6):439-54. doi: 10.2217/nmt.14.34. PMID: 25531687Free PMC Article
Fernández-Matarrubia M, Matías-Guiu JA, Moreno-Ramos T, Matías-Guiu J
Neurologia 2014 Oct;29(8):464-72. Epub 2013 May 4 doi: 10.1016/j.nrl.2013.03.001. PMID: 23648383

Recent systematic reviews

Guay-Gagnon M, Vat S, Forget MF, Tremblay-Gravel M, Ducharme S, Nguyen QD, Desmarais P
J Sleep Res 2022 Oct;31(5):e13589. Epub 2022 Apr 2 doi: 10.1111/jsr.13589. PMID: 35366021
Ossenkoppele R, Singleton EH, Groot C, Dijkstra AA, Eikelboom WS, Seeley WW, Miller B, Laforce RJ, Scheltens P, Papma JM, Rabinovici GD, Pijnenburg YAL
JAMA Neurol 2022 Jan 1;79(1):48-60. doi: 10.1001/jamaneurol.2021.4417. PMID: 34870696Free PMC Article
Arevalo-Rodriguez I, Smailagic N, Roqué-Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A, Pedraza OL, Bonfill Cosp X, Cullum S
Cochrane Database Syst Rev 2021 Jul 27;7(7):CD010783. doi: 10.1002/14651858.CD010783.pub3. PMID: 34313331Free PMC Article
McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, Maayan N, Ware J, Debarros J
Cochrane Database Syst Rev 2019 Mar 20;3(3):CD003154. doi: 10.1002/14651858.CD003154.pub6. PMID: 30891742Free PMC Article
Creavin ST, Wisniewski S, Noel-Storr AH, Trevelyan CM, Hampton T, Rayment D, Thom VM, Nash KJ, Elhamoui H, Milligan R, Patel AS, Tsivos DV, Wing T, Phillips E, Kellman SM, Shackleton HL, Singleton GF, Neale BE, Watton ME, Cullum S
Cochrane Database Syst Rev 2016 Jan 13;2016(1):CD011145. doi: 10.1002/14651858.CD011145.pub2. PMID: 26760674Free PMC Article

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    Clinical resources

    Practice guidelines

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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2023
      UK NICE Clinical guideline (CG148), Urinary incontinence in neurological disease: assessment and management, 2023

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