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Parkinsonism

MedGen UID:
504793
Concept ID:
CN001191
Finding
Synonyms: Parkinsonian disease
 
HPO: HP:0001300

Definition

Characteristic neurologic anomaly resulting form 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. [from HPO]

Conditions with this feature

Alzheimer disease
MedGen UID:
1853
Concept ID:
C0002395
Disease or Syndrome
Alzheimer disease (AD) is characterized by dementia that typically begins with subtle and poorly recognized failure of memory and slowly becomes more severe and, eventually, incapacitating. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations. Occasionally, seizures, Parkinsonian features, increased muscle tone, myoclonus, incontinence, and mutism occur. Death usually results from general inanition, malnutrition, and pneumonia. The typical clinical duration of the disease is eight to ten years, with a range from one to 25 years. Approximately 25% of all AD is familial (i.e., =2 persons in a family have AD) of which approximately 95% is late onset (age >60-65 years) and 5% is early onset (age <65 years).
Gerstmann-Straussler-Scheinker syndrome
MedGen UID:
4886
Concept ID:
C0017495
Disease or Syndrome
Genetic prion diseases generally manifest with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease. Note: A fourth clinical phenotype, known as Huntington disease like-1 (HDL-1) has been proposed, but this is based on a single report, and the underlying pathologic features would categorize it as GSS. Although it is clear that these four subtypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset ranges from the third to ninth decade of life. The course ranges from a few months to several years (typically 5-7 years; in rare instances, >10 years).
Pigmentary pallidal degeneration
MedGen UID:
6708
Concept ID:
C0018523
Disease or Syndrome
Pantothenate kinase-associated neurodegeneration (PKAN) is a form of neurodegeneration with brain iron accumulation, or NBIA (formerly called Hallervorden-Spatz syndrome). PKAN is characterized by progressive dystonia and basal ganglia iron deposition with onset that usually occurs before age ten years. Commonly associated features include dysarthria, rigidity, and pigmentary retinopathy. Approximately 25% of affected individuals have an 'atypical' presentation with later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease.
Azorean disease
MedGen UID:
9841
Concept ID:
C0024408
Disease or Syndrome
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is characterized by progressive cerebellar ataxia and variable findings including a dystonic-rigid syndrome, a parkinsonian syndrome, or a combined syndrome of dystonia and peripheral neuropathy. Neurologic findings tend to evolve as the disease progresses.
Shy-Drager syndrome
MedGen UID:
20740
Concept ID:
C0037019
Disease or Syndrome
Multiple system atrophy (MSA) is a distinct clinicopathologic entity that manifests as a progressive adult-onset neurodegenerative disorder causing parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Two main subtypes are recognized: 'subtype C,' characterized predominantly by cerebellar ataxia, and 'subtype P,' characterized predominantly by parkinsonism. MSA is characterized pathologically by the degeneration of striatonigral and olivopontocerebellar structures and glial cytoplasmic inclusions that consist of abnormally phosphorylated alpha-synuclein (SNCA; 163890) or tau (MAPT; 157140) (Gilman et al., 1998; Gilman et al., 2008; Scholz et al., 2009). 'Subtype C' of MSA has been reported to be more prevalent than 'subtype P' in the Japanese population (65-67% vs 33-35%), whereas 'subtype P' has been reported to be more prevalent than 'subtype C' in Europe (63% vs 34%) and North America (60% vs 13%, with 27% of cases unclassified) (summary by The Multiple-System Atrophy Research Collaboration, 2013). MSA is similar clinically and pathologically to Parkinson disease (PD; 168600) and Lewy body dementia (127750). See also PARK1 (168601), which is specifically caused by mutation in the SNCA gene. Pure autonomic failure manifests as orthostatic hypotension and other autonomic abnormalities without other neurologic involvement. Although there is some phenotypic overlap, the relationship of pure autonomic failure to MSA is unclear (Vanderhaeghen et al., 1970; Schatz, 1996).
Progressive supranuclear ophthalmoplegia
MedGen UID:
21026
Concept ID:
C0038868
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.
Pick disease
MedGen UID:
116020
Concept ID:
C0236642
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.
Juvenile paralysis agitans of Hunt
MedGen UID:
66768
Concept ID:
C0238344
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
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.
Choreoacanthocytosis
MedGen UID:
98277
Concept ID:
C0393576
Disease or Syndrome
Chorea-acanthocytosis (ChAc) is characterized by a progressive movement disorder, cognitive and behavior changes, a myopathy that can be subclinical, and chronic hyperCKemia in serum. Although the disorder is named for acanthocytosis of the red blood cells, this feature is variable. The movement disorder is mostly limb chorea, but some individuals present with parkinsonism. Dystonia is common and affects the oral region and especially the tongue, causing dysarthria and serious dysphagia with resultant weight loss. Habitual tongue and lip biting are characteristic, as well as tongue protrusion dystonia. Progressive cognitive and behavioral changes resemble those in a frontal lobe syndrome. Seizures are observed in almost half of affected individuals and can be the initial manifestation. Myopathy results in progressive distal muscle wasting and weakness. Mean age of onset in ChAc is about 30 years, although ChAc can develop as early as the first decade or as late as the seventh decade. It runs a chronic progressive course and may lead to major disability within a few years. Life expectancy is reduced, with age of death ranging from 28 to 61 years.
Idiopathic basal ganglia calcification 1
MedGen UID:
97952
Concept ID:
C0393590
Disease or Syndrome
Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with gradually progressive neuropsychiatric and movement disorders. The main manifestations include clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Migraine is frequent and seizures of various types may also occur. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia.
Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1
MedGen UID:
107775
Concept ID:
C0543859
Disease or Syndrome
Amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam is a neurodengenerative disorder with unusually high incidence among the Chamorro people of Guam. Both ALS and parkinsonism-dementia are chronic, progressive, and uniformly fatal disorders in this population. Both diseases are known to occur in the same kindred, the same sibship, and even the same individual.
Juvenile neuronal ceroid lipofuscinosis
MedGen UID:
155549
Concept ID:
C0751383
Disease or Syndrome
The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death. Visual loss is a feature of most forms. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features into infantile, late-infantile, juvenile, adult, and Northern epilepsy (also known as progressive epilepsy with mental retardation [EPMR]). There is however genetic and allelic heterogeneity; a proposed new nomenclature and classification system has been developed to take into account both the responsible gene and the age at disease onset; for example, CLN1 disease, infantile onset and CLN1 disease, juvenile onset are both caused by pathogenic variants in PPT1 but with differing age of onset. The most prevalent NCLs are CLN3 disease, classic juvenile and CLN2 disease, classic late infantile (although prevalence varies by ethnicity and country of family origin): CLN2 disease, classic late infantile. The first symptoms typically appear between age two and four years, usually starting with epilepsy, followed by regression of developmental milestones, myoclonic ataxia, and pyramidal signs. Visual impairment typically appears at age four to six years and rapidly progresses to light /dark awareness only. Life expectancy ranges from age six years to early teenage. CLN3 disease, classic juvenile. Onset is usually between ages four and ten years. Rapidly progressing visual loss resulting in severe visual impairment within one to two years is often the first clinical sign. Epilepsy with generalized tonic-clonic seizures and/or complex-partial seizures typically appears around age ten years. Life expectancy ranges from the late teens to the 30s. Other forms of NCL may present with behavior changes, epilepsy, visual impairment, or slowing of developmental progress and then loss of skills. The course may be extremely variable. Some genotype-phenotype information is available.
Lewy body dementia
MedGen UID:
199874
Concept ID:
C0752347
Disease or Syndrome
Dementia with Lewy bodies (DLB) is a neurodegenerative disorder clinically characterized by dementia and parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Pathologically, Lewy bodies are present in a pattern more widespread than usually observed in Parkinson disease (see PD; 168600). Alzheimer disease (AD; 104300)-associated pathology and spongiform changes may also be seen (McKeith et al., 1996; Mizutani, 2000; McKeith et al., 2005).
Parkinsonism, early onset with mental retardation
MedGen UID:
208674
Concept ID:
C0796195
Disease or Syndrome
Waisman syndrome is an X-linked neurologic disorder characterized by delayed psychomotor development, intellectual disability, and early-onset Parkinson disease (summary by Wilson et al., 2014).
6-pyruvoyl-tetrahydropterin synthase deficiency
MedGen UID:
209234
Concept ID:
C0878676
Disease or Syndrome
Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH; 612349), tyrosine hydroxylase (TH; 191290) and tryptophan hydroxylase (TPH1; 191060), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001). HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (233910), caused by mutation in the GCH1 gene (600225), HPABH4C (261630), caused by mutation in the QDPR gene (612676), and HPABH4D (264070), caused by mutation in the PCBD1 gene (126090). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU; 261600), caused by mutation in the PAH gene. Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (612716), caused by mutation in the SPR gene (182125), and autosomal dominant dopa-responsive dystonia (DYT5; 128230), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.
Ceroid lipofuscinosis neuronal 4B autosomal dominant
MedGen UID:
320287
Concept ID:
C1834207
Disease or Syndrome
The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death. Visual loss is a feature of most forms. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features into infantile, late-infantile, juvenile, adult, and Northern epilepsy (also known as progressive epilepsy with mental retardation [EPMR]). There is however genetic and allelic heterogeneity; a proposed new nomenclature and classification system has been developed to take into account both the responsible gene and the age at disease onset; for example, CLN1 disease, infantile onset and CLN1 disease, juvenile onset are both caused by pathogenic variants in PPT1 but with differing age of onset. The most prevalent NCLs are CLN3 disease, classic juvenile and CLN2 disease, classic late infantile (although prevalence varies by ethnicity and country of family origin): CLN2 disease, classic late infantile. The first symptoms typically appear between age two and four years, usually starting with epilepsy, followed by regression of developmental milestones, myoclonic ataxia, and pyramidal signs. Visual impairment typically appears at age four to six years and rapidly progresses to light /dark awareness only. Life expectancy ranges from age six years to early teenage. CLN3 disease, classic juvenile. Onset is usually between ages four and ten years. Rapidly progressing visual loss resulting in severe visual impairment within one to two years is often the first clinical sign. Epilepsy with generalized tonic-clonic seizures and/or complex-partial seizures typically appears around age ten years. Life expectancy ranges from the late teens to the 30s. Other forms of NCL may present with behavior changes, epilepsy, visual impairment, or slowing of developmental progress and then loss of skills. The course may be extremely variable. Some genotype-phenotype information is available.
Supranuclear palsy, progressive, 2
MedGen UID:
324446
Concept ID:
C1836148
Disease or Syndrome
Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after the other movement problems first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living.
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3
MedGen UID:
373087
Concept ID:
C1836439
Disease or Syndrome
Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Patients with C10ORF2-linked adPEO may have other clinical features including proximal muscle weakness, ataxia, peripheral neuropathy, cardiomyopathy, cataracts, depression, and endocrine abnormalities (summary by Fratter et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640). PEO caused by mutations in the POLG gene are associated with more complicated phenotypes than those forms caused by mutations in the SLC25A4 (103220) or C10ORF2 genes (Lamantea et al., 2002).
Alzheimer disease, susceptibility to, mitochondrial
MedGen UID:
325148
Concept ID:
C1838990
Finding
Fragile X tremor/ataxia syndrome
MedGen UID:
333403
Concept ID:
C1839780
Disease or Syndrome
FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related primary ovarian insufficiency (POI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Because FMR1 pathogenic variants are complex alterations involving non-classic gene-disrupting alterations (trinucleotide repeat expansion) and abnormal gene methylation, affected individuals occasionally have an atypical presentation with an IQ above 70, the traditional demarcation denoting intellectual disability (previously referred to as mental retardation). Males with an FMR1 full mutation accompanied by aberrant methylation may have a characteristic appearance (large head, long face, prominent forehead and chin, protruding ears), connective tissue findings (joint laxity), and large testes after puberty. Behavioral abnormalities, sometimes including autism spectrum disorder, are common. FXTAS occurs in males (and some females) who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor. FMR1-related POI (age at cessation of menses <40 years) occurs in approximately 20% of females who have an FMR1 premutation.
Alzheimer disease, type 3
MedGen UID:
334304
Concept ID:
C1843013
Disease or Syndrome
Alzheimer disease (AD) is characterized by adult-onset progressive dementia associated with cerebral cortical atrophy, beta-amyloid plaque formation, and intraneuronal neurofibrillary tangles. AD typically begins with subtle memory failure that becomes more severe and is eventually incapacitating. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, hallucinations, seizures, Parkinsonian features, increased muscle tone, myoclonus, incontinence, and mutism. Familial AD (FAD) characterizes families that have more than one member with AD and usually implies multiple affected persons in more than one generation. Early-onset FAD (EOFAD) refers to families in which onset is consistently before age 60 to 65 years and often before age 55 years.
Alzheimer disease, familial, 3, with spastic paraparesis and unusual plaques
MedGen UID:
375073
Concept ID:
C1843014
Disease or Syndrome
Alzheimer disease, familial, 3, with spastic paraparesis and apraxia
MedGen UID:
334659
Concept ID:
C1843015
Disease or Syndrome
Frontotemporal dementia, ubiquitin-positive
MedGen UID:
375285
Concept ID:
C1843792
Disease or Syndrome
The spectrum of frontotemporal dementia associated with GRN (also known as PGRN) mutation (FTD-GRN or FTD-PGRN) includes the behavioral variant (FTD-bv), primary progressive aphasia (PPA; further sub-categorized as progressive non-fluent aphasia [PNFA] and semantic dementia [SD]), and movement disorders with extrapyramidal features such as parkinsonism and corticobasal syndrome. A broad range of clinical features both within and across 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.
Spinocerebellar ataxia 21
MedGen UID:
375311
Concept ID:
C1843891
Disease or Syndrome
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.
Spinocerebellar ataxia 17
MedGen UID:
337637
Concept ID:
C1846707
Disease or Syndrome
Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course.
Parkinson disease 9
MedGen UID:
338281
Concept ID:
C1847640
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Parkinson-dementia syndrome
MedGen UID:
337962
Concept ID:
C1850076
Disease or Syndrome
Cerebellar ataxia infantile with progressive external ophthalmoplegia
MedGen UID:
340509
Concept ID:
C1850303
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. These phenotypes exemplify the diversity that can result from mutation of a given gene. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life up to about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, Parkinsonism, hypogonadism, and cataracts (in what has been called “chronic progressive external ophthalmoplegia plus,” or “CPEO+”).
Dystonia 5, Dopa-responsive type
MedGen UID:
342121
Concept ID:
C1851920
Disease or Syndrome
GTP cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) is characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of oral administration of levodopa. The average age of onset is approximately six years. This disorder typically presents with gait disturbance caused by foot dystonia, later development of parkinsonism, and diurnal fluctuation of symptoms (aggravation of symptoms toward the evening and alleviation of symptoms in the morning after sleep). Initial symptoms are often gait difficulties attributable to flexion-inversion (equinovarus posture) of the foot. Occasionally, initial symptoms are arm dystonia, postural tremor of the hand, or slowness of movements. Brisk deep-tendon reflexes in the legs, ankle clonus, and/or the striatal toe (dystonic extension of the big toe) are present in many affected individuals. In general, gradual progression to generalized dystonia is observed. Intellectual, cerebellar, sensory, and autonomic disturbances generally do not occur.
Dementia/parkinsonism with non-alzheimer amyloid plaques
MedGen UID:
338883
Concept ID:
C1852223
Disease or Syndrome
Spinocerebellar ataxia 28
MedGen UID:
339941
Concept ID:
C1853249
Disease or Syndrome
Spinocerebellar ataxia type 28 (SCA28) is characterized by young-adult onset, slowly progressive gait and limb ataxia, dysarthria, hyperreflexia of the lower limbs, nystagmus, and ophthalmoparesis. The usual age at onset is early adulthood (24.4 ± 14.9 years); range is from age three to 60 years. The course of the disease is slowly progressive without impairment of functional autonomy even decades after onset.
Neuroferritinopathy
MedGen UID:
381211
Concept ID:
C1853578
Disease or Syndrome
Neuroferritinopathy typically presents with progressive adult-onset chorea or dystonia affecting one or two limbs, and subtle cognitive deficits. The movement disorder involves additional limbs within five to ten years and becomes more generalized within 20 years. When present, asymmetry remains throughout the course of the disorder. The majority of individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time.
Parkinson disease 6, autosomal recessive early-onset
MedGen UID:
342982
Concept ID:
C1853833
Disease or Syndrome
The PINK1 type of young-onset Parkinson disease is characterized by variable combinations of rigidity, bradykinesia, and rest tremor, often making it clinically indistinguishable from idiopathic Parkinson disease. Lower-limb dystonia may be a presenting sign. Onset usually occurs in the third or fourth decade. The disease is slowly progressive. Clinical signs vary; hyperreflexia may be present and abnormal behavior and/or psychiatric manifestations have been described. Dyskinesias as a result of treatment with levodopa frequently occur, as with all individuals with young-onset disease, regardless of the underlying genetic cause.
Parkinson disease 4
MedGen UID:
381361
Concept ID:
C1854182
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Segawa syndrome, autosomal recessive
MedGen UID:
343087
Concept ID:
C1854299
Disease or Syndrome
Tyrosine hydroxylase (TH) deficiency is associated with a broad phenotypic spectrum. Based on severity of symptoms/signs as well as responsiveness to levodopa therapy, clinical phenotypes caused by TH pathogenic variants are divided into (1) TH-deficient dopa-responsive dystonia (DRD: the mild form of TH deficiency [DYT5b]), (2) TH-deficient infantile parkinsonism with motor delay (the severe form), and (3) TH-deficient progressive infantile encephalopathy (the very severe form). In individuals with TH-deficient DRD, onset is between age 12 months and six years; initial symptoms are typically lower-limb dystonia and/or difficulty in walking. Diurnal fluctuation of symptoms (worsening of the symptoms toward the evening and their alleviation in the morning after sleep) may be present. In most individuals with TH-deficient infantile parkinsonism with motor delay, onset is between age three and 12 months. In contrast to TH-deficient DRD, motor milestones are overtly delayed in this severe form. Affected infants demonstrate truncal hypotonia and parkinsonian symptoms and signs (hypokinesia, rigidity of extremities, and/or tremor). In individuals with TH-deficient progressive infantile encephalopathy, onset is before age three to six months. Fetal distress is reported in most. Affected individuals have marked delay in motor development, truncal hypotonia, severe hypokinesia, limb hypertonia (rigidity and/or spasticity), hyperreflexia, oculogyric crises, ptosis, mental retardation, and paroxysmal periods of lethargy (with increased sweating and drooling) alternating with irritability.
Spinocerebellar ataxia 12
MedGen UID:
347653
Concept ID:
C1858501
Disease or Syndrome
Spinocerebellar ataxia type 12 (SCA12) is characterized by onset of action tremor of the upper extremities in the fourth decade, slowly progressing to include ataxia and other cerebellar and cortical signs. Given the small number of individuals known to have SCA12, it is possible that other clinical manifestations have not yet been recognized.
Spastic paraplegia 10
MedGen UID:
349003
Concept ID:
C1858712
Disease or Syndrome
Spastic paraplegia-10 is an autosomal dominant neurologic disorder with variable manifestations. Some patients have onset of a 'pure' spastic paraplegia, with lower limb spasticity, hyperreflexia, extensor plantar responses, and variable involvement of the upper limbs beginning in childhood or young adulthood. Some patients show distal sensory impairment, which can be part of the 'pure' phenotype. However, some patients also show an axonal sensorimotor peripheral neuropathy with distal sensory impairment and distal muscle atrophy reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A, 118210). Rarely, patients with KIF5A mutations may have additional neurologic features, including parkinsonism or cognitive decline, consistent with a 'complicated' phenotype. Spastic paraplegia and peripheral neuropathy in isolation may represent extreme ends of the phenotypic spectrum of KIF5A mutations (summary by Goizet et al., 2009 and Crimella et al., 2012).
Charcot-Marie-Tooth disease with ptosis and parkinsonism
MedGen UID:
396191
Concept ID:
C1861668
Disease or Syndrome
Frontotemporal dementia and/or amyotrophic lateral sclerosis
MedGen UID:
350795
Concept ID:
C1862937
Disease or Syndrome
Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) is an autosomal dominant neurodegenerative disorder characterized by adult onset of one or both of these features in an affected individual, with significant intrafamilial variation. The disorder is genetically and pathologically heterogeneous (summary by Vance et al., 2006). Patients with C9ORF72 repeat expansions tend to show a lower age of onset, shorter survival, bulbar symptom onset, increased incidence of neurodegenerative disease in relatives, and a propensity toward psychosis or hallucinations compared to patients with other forms of ALS and/or FTD (summary by Harms et al., 2013). Patients with C9ORF72 repeat expansions also show psychiatric disturbances that may predate the onset of dementia (Meisler et al., 2013; Gomez-Tortosa et al., 2013). For a general phenotypic description of frontotemporal dementia, also known as frontotemporal lobar degeneration (FTLD), see 600274. For a general discussion of motor neuron disease (MND), see amyotrophic lateral sclerosis-1 (ALS1; 105400). Genetic Heterogeneity of Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis See also FTDALS2 (615911), caused by mutation in the CHCHD10 gene (615903) on chromosome 22q11; FTDALS3 (616437), caused by mutation in the SQSTM1 gene (601530) on chromosome 5q35; and FTDALS4 (616439), caused by mutation in the TBK1 gene (604834) on chromosome 12q14.
Alzheimer disease 2
MedGen UID:
400197
Concept ID:
C1863051
Disease or Syndrome
Alzheimer disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood.Memory loss is the most common sign of Alzheimer disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.As the disorder progresses, some people with Alzheimer disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with this disease usually require total care during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting (inanition).Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease.
Perry syndrome
MedGen UID:
357007
Concept ID:
C1868594
Disease or Syndrome
Perry syndrome is characterized by parkinsonism, hypoventilation, depression, and weight loss. The mean age at onset is 49 years; the mean disease duration is five years. Parkinsonism and psychiatric changes (depression, apathy, character changes, and withdrawal) tend to occur early; severe weight loss and hypoventilation manifest later.
Parkinson disease 1
MedGen UID:
357008
Concept ID:
C1868595
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Parkinson disease 2
MedGen UID:
401500
Concept ID:
C1868675
Disease or Syndrome
Parkin type of early-onset Parkinson disease is characterized by rigidity, bradykinesia, and resting tremor. Lower-limb dystonia may be a presenting sign. Onset usually occurs between ages 20 and 40 years with an average age of onset in the early to mid-thirties. The disease is slowly progressive and disease duration of more than 50 years has been reported. Clinical signs vary; hyperreflexia is common. Dyskinesia as a result of treatment with levodopa frequently occurs.
Dystonia 12
MedGen UID:
358384
Concept ID:
C1868681
Disease or Syndrome
The spectrum of ATP1A3-related neurologic disorders includes rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome. While early reports emphasized the distinctness of RDP and AHC, it is increasingly evident that these conditions represent a spectrum related to mutation of ATP1A3. Because only ten individuals from three families and one individual with a de novo mutation have been described with CAPOS syndrome to date, its phenotype is less defined; however, some features overlap with RDP and AHC as well. RDP is characterized by abrupt onset of dystonia with parkinsonism (primarily bradykinesia and postural instability); a clear rostrocaudal (face>arm>leg) topological gradient of involvement; bulbar involvement; and absence of response to an adequate trial of L-dopa therapy. Often fever, physiologic stress, or alcoholic binges trigger the onset of symptoms. After their initial appearance, symptoms often stabilize with little improvement; occasionally second episodes occur with abrupt worsening of symptoms. Anxiety, depression, and seizures have been reported. Age of onset is four to 55 years. AHC is a complex neurodevelopmental syndrome most frequently manifesting in infancy or early childhood with paroxysmal episodic neurologic dysfunction including alternating hemiparesis or dystonia, quadriparesis, seizure-like episodes, and oculomotor abnormalities. Episodes can last for minutes, hours, days, or even weeks. Remission of symptoms occurs with sleep and immediately after awakening. Over time, persistent neurologic deficits develop in the majority of those affected, including oculomotor apraxia, ataxia, choreoathetosis, dystonia, parkinsonism, and cognitive and behavioral dysfunction; more than 50% develop epilepsy in addition to their episodic movement disorder phenotype. CAPOS syndrome (a mnemonic for cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing loss) is characterized by episodes of ataxic encephalopathy and/or weakness after a febrile illness. Onset is between ages six months and five years. Some acute symptoms resolve; disease progression and severity vary.
Mental retardation, X-linked, syndromic 13
MedGen UID:
368466
Concept ID:
C1968550
Disease or Syndrome
The MECP2 gene is mutated in Rett syndrome (RTT; 312750), a severe neurodevelopmental disorder that almost always occurs in females. Males with non-RTT mutations in the MECP2 gene can demonstrate a wide variety of phenotypes, including X-linked mental retardation with spasticity and other variable features, described here, and Lubs X-linked mental retardation syndrome (MRXSL; 300260). Males with RTT-associated MECP2 mutations have neonatal severe encephalopathy that is usually lethal (300673) (Moog et al., 2003; Villard, 2007).
Dystonia 16
MedGen UID:
436979
Concept ID:
C2677567
Disease or Syndrome
Hypermanganesemia with dystonia, polycythemia and cirrhosis
MedGen UID:
412958
Concept ID:
C2750442
Disease or Syndrome
The disorder dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is characterized by the following: A movement disorder resulting from manganese accumulation in the basal ganglia. Whole-blood manganese concentrations that often exceed 2000 nmol/L (normal: <320 nmol/L). Polycythemia. Hepatomegaly with variable hepatic fibrosis/cirrhosis. Neurologic findings can manifest either in childhood (ages 2-15 years) as four-limb dystonia, leading to a characteristic high-stepping gait (“cock-walk gait”), dysarthria, fine tremor, and bradykinesia or on occasion spastic paraplegia, or in adulthood as parkinsonism (shuffling gait, rigidity, bradykinesia, hypomimia, and monotone speech) unresponsive to L-dopa treatment. Hepatic failure, secondary complications of cirrhosis, and the neurologic disorder shorten life expectancy.
Infantile Parkinsonism-dystonia
MedGen UID:
413468
Concept ID:
C2751067
Disease or Syndrome
Infantile parkinsonism-dystonia, also known as dopamine transporter deficiency syndrome (DTDS), is an autosomal recessive complex motor neurologic disorder with onset in infancy. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, pyramidal tract signs, and eye movement abnormalities. Many patients are misdiagnosed as having cerebral palsy. Cognitive function appears to be less severely affected, but most patients die in the teenage years. There is no effective treatment. Laboratory studies show an increased ratio of homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), which represents an increase in dopamine metabolites (review by Kurian et al., 2011). For an overlapping phenotype, see tyrosine hydroxylase deficiency (605407), also known as autosomal recessive Segawa syndrome.
Parkinson disease 14
MedGen UID:
414488
Concept ID:
C2751842
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Acne inversa, familial, 3
MedGen UID:
462388
Concept ID:
C3151038
Disease or Syndrome
Acne inversa is a chronic inflammatory disease of the hair follicles whose characteristic features include draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Familial acne inversa is genetically heterogeneous (summary by Wang et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of familial acne inversa, see 142690.
Parkinson disease, late-onset
MedGen UID:
463618
Concept ID:
C3160718
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Cardiomyopathy, dilated, 1u
MedGen UID:
463620
Concept ID:
C3160720
Disease or Syndrome
Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal nocturnal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke.
Parkinson disease 17
MedGen UID:
481763
Concept ID:
C3280133
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Parkinson disease 18
MedGen UID:
481901
Concept ID:
C3280271
Disease or Syndrome
Parkinson disease-18 is an autosomal dominant, adult-onset form of the disorder. It is phenotypically similar to idiopathic Parkinson disease (summary by Chartier-Harlin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600.
Neurodegeneration with brain iron accumulation 4
MedGen UID:
482001
Concept ID:
C3280371
Disease or Syndrome
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is characterized initially by gait changes followed by progressive spastic paresis, progressive dystonia (which may be limited to the hands and feet or more generalized), neuropsychiatric abnormalities (e.g., emotional lability, depression, anxiety, impulsivity, compulsions, hallucinations, perseveration, inattention, and hyperactivity), and cognitive decline. Additional early findings can include dysphagia, dysarthria, optic atrophy, axonal neuropathy, parkinsonism, and bowel/bladder incontinence. Survival is usually well into adulthood. End-stage disease is characterized by severe dementia, spasticity, dystonia, and parkinsonism.
Neurodegeneration with brain iron accumulation 5
MedGen UID:
763887
Concept ID:
C3550973
Disease or Syndrome
NBIA5, sometimes referred to as 'static encephalopathy of childhood with neurodegeneration in adulthood (SENDA),' is an X-linked neurodegenerative disorder characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability. Brain MRI shows iron accumulation in the globus pallidus and substantia nigra. A characteristic finding is T1-weighted hyperintensity surrounding a central band of hypointensity in the substantia nigra. Cerebral and cerebellar atrophy are also observed (summary by Haack et al., 2012 and Saitsu et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (234200).
Basal ganglia calcification, idiopathic, 4
MedGen UID:
767235
Concept ID:
C3554321
Disease or Syndrome
Idiopathic basal ganglia calcification-4 is an autosomal dominant condition characterized by the accumulation of calcium deposits in various brain regions, most commonly in the basal ganglia. About half of mutation carriers are asymptomatic, but some present later in life with parkinsonism and impaired cognitive function. Migraine or depression may occur in younger individuals (summary by Nicolas et al., 2013). For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).
Parkinsonism with spasticity, X-linked
MedGen UID:
813052
Concept ID:
C3806722
Disease or Syndrome
Idiopathic basal ganglia calcification 5
MedGen UID:
815975
Concept ID:
C3809645
Disease or Syndrome
Idiopathic basal ganglia calcification-5 (IBGC5) is an autosomal dominant disorder characterized by progressive neurologic symptoms that are associated with brain calcifications mainly affecting the basal ganglia. Calcifications may also occur in the thalamus, cerebellum, or white matter. Affected individuals have motor symptoms, such as dyskinesias or parkinsonism, headache, cognitive impairment, and psychiatric manifestations, including apathy and depression. Some patients are asymptomatic. The age at symptom onset ranges from late childhood to adulthood; the disorder is progressive (summary by Keller et al., 2013). For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).
Parkinson disease 19a, juvenile-onset
MedGen UID:
816141
Concept ID:
C3809811
Disease or Syndrome
Parkinson disease-19A is an autosomal recessive neurodegenerative disorder characterized by onset of parkinsonism in the first or second decade. Some patients may have additional neurologic features, including mental retardation and seizures (summary by Edvardson et al., 2012 and Koroglu et al., 2013). Parkinson disease-19B is an autosomal recessive neurodegenerative disorder with onset of parkinsonism between the third and fifth decades. It is slowly progressive, shows features similar to classic late-onset Parkinson disease (PD), and has a beneficial response to dopaminergic therapy (Olgiati et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
Parkinson disease 20, early-onset
MedGen UID:
816154
Concept ID:
C3809824
Disease or Syndrome
Parkinson disease-20 is an autosomal recessive neurodegenerative disorder characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia (summary by Krebs et al., 2013 and Quadri et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 2
MedGen UID:
863085
Concept ID:
C4014648
Disease or Syndrome
Alzheimer disease, familial, with spastic paraparesis and unusual plaques
MedGen UID:
864217
Concept ID:
C4015780
Finding
Alzheimer disease, familial, 3, with unusual plaques
MedGen UID:
864218
Concept ID:
C4015781
Finding
Alzheimer disease familial 3, with spastic paraparesis
MedGen UID:
864219
Concept ID:
C4015782
Finding

Recent clinical studies

Etiology

Buchman AS, Wilson RS, Shulman JM, Leurgans SE, Schneider JA, Bennett DA
J Gerontol A Biol Sci Med Sci 2016 Apr;71(4):549-56. Epub 2015 Sep 10 doi: 10.1093/gerona/glv153. PMID: 26362440Free PMC Article
Hwang I, Sohn CH, Kang KM, Jeon BS, Kim HJ, Choi SH, Yun TJ, Kim JH
AJNR Am J Neuroradiol 2015 Dec;36(12):2227-34. Epub 2015 Sep 3 doi: 10.3174/ajnr.A4442. PMID: 26338919
Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Weerkamp NJ, Tissingh G, Poels PJ, Zuidema SU, Munneke M, Koopmans RT, Bloem BR
Parkinsonism Relat Disord 2014 Nov;20(11):1157-60. Epub 2014 Aug 28 doi: 10.1016/j.parkreldis.2014.07.017. PMID: 25258327
Morley JF, Pawlowski SM, Kesari A, Maina I, Pantelyat A, Duda JE
Parkinsonism Relat Disord 2014 Jul;20(7):738-42. Epub 2014 Apr 1 doi: 10.1016/j.parkreldis.2014.03.024. PMID: 24742370

Diagnosis

van der Holst HM, van Uden IW, Tuladhar AM, de Laat KF, van Norden AG, Norris DG, van Dijk EJ, Esselink RA, Platel B, de Leeuw FE
Neurology 2015 Nov 3;85(18):1569-77. Epub 2015 Oct 7 doi: 10.1212/WNL.0000000000002082. PMID: 26446068Free PMC Article
Hwang I, Sohn CH, Kang KM, Jeon BS, Kim HJ, Choi SH, Yun TJ, Kim JH
AJNR Am J Neuroradiol 2015 Dec;36(12):2227-34. Epub 2015 Sep 3 doi: 10.3174/ajnr.A4442. PMID: 26338919
Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Weerkamp NJ, Tissingh G, Poels PJ, Zuidema SU, Munneke M, Koopmans RT, Bloem BR
Parkinsonism Relat Disord 2014 Nov;20(11):1157-60. Epub 2014 Aug 28 doi: 10.1016/j.parkreldis.2014.07.017. PMID: 25258327
Morley JF, Pawlowski SM, Kesari A, Maina I, Pantelyat A, Duda JE
Parkinsonism Relat Disord 2014 Jul;20(7):738-42. Epub 2014 Apr 1 doi: 10.1016/j.parkreldis.2014.03.024. PMID: 24742370

Therapy

Chang CC, Hsiao IT, Huang SH, Lui CC, Yen TC, Chang WN, Huang CW, Hsieh CJ, Chang YY, Lin KJ
Eur J Neurol 2015 May;22(5):845-52, e59-60. Epub 2015 Feb 18 doi: 10.1111/ene.12672. PMID: 25690304
Chun MH, Kang CG, Kong EJ, Chang MC
J Stroke Cerebrovasc Dis 2015 Mar;24(3):e75-8. Epub 2014 Oct 30 doi: 10.1016/j.jstrokecerebrovasdis.2014.10.013. PMID: 25543190
Quiroga MJ, Carroll DW, Brown TM
Ann Pharmacother 2014 Nov;48(11):1515-20. Epub 2014 Jul 28 doi: 10.1177/1060028014545356. PMID: 25070397
Morley JF, Pawlowski SM, Kesari A, Maina I, Pantelyat A, Duda JE
Parkinsonism Relat Disord 2014 Jul;20(7):738-42. Epub 2014 Apr 1 doi: 10.1016/j.parkreldis.2014.03.024. PMID: 24742370
Tinazzi M, Morgante F, Matinella A, Bovi T, Cannas A, Solla P, Marrosu F, Nicoletti A, Zappia M, Luca A, Di Stefano A, Morgante L, Pacchetti C, Minafra B, Sciarretta M, Dallocchio C, Rossi S, Ulivelli M, Ceravolo R, Frosini D, Cipriani A, Barbui C
Schizophr Res 2014 Feb;152(2-3):344-9. Epub 2013 Dec 25 doi: 10.1016/j.schres.2013.11.028. PMID: 24369987

Prognosis

van der Holst HM, van Uden IW, Tuladhar AM, de Laat KF, van Norden AG, Norris DG, van Dijk EJ, Esselink RA, Platel B, de Leeuw FE
Neurology 2015 Nov 3;85(18):1569-77. Epub 2015 Oct 7 doi: 10.1212/WNL.0000000000002082. PMID: 26446068Free PMC Article
Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Weerkamp NJ, Tissingh G, Poels PJ, Zuidema SU, Munneke M, Koopmans RT, Bloem BR
Parkinsonism Relat Disord 2014 Nov;20(11):1157-60. Epub 2014 Aug 28 doi: 10.1016/j.parkreldis.2014.07.017. PMID: 25258327
Brigo F, Erro R, Marangi A, Bhatia K, Tinazzi M
Parkinsonism Relat Disord 2014 Aug;20(8):808-14. Epub 2014 Jun 3 doi: 10.1016/j.parkreldis.2014.05.011. PMID: 24935237
Morley JF, Pawlowski SM, Kesari A, Maina I, Pantelyat A, Duda JE
Parkinsonism Relat Disord 2014 Jul;20(7):738-42. Epub 2014 Apr 1 doi: 10.1016/j.parkreldis.2014.03.024. PMID: 24742370

Clinical prediction guides

van der Holst HM, van Uden IW, Tuladhar AM, de Laat KF, van Norden AG, Norris DG, van Dijk EJ, Esselink RA, Platel B, de Leeuw FE
Neurology 2015 Nov 3;85(18):1569-77. Epub 2015 Oct 7 doi: 10.1212/WNL.0000000000002082. PMID: 26446068Free PMC Article
Hwang I, Sohn CH, Kang KM, Jeon BS, Kim HJ, Choi SH, Yun TJ, Kim JH
AJNR Am J Neuroradiol 2015 Dec;36(12):2227-34. Epub 2015 Sep 3 doi: 10.3174/ajnr.A4442. PMID: 26338919
Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Brigo F, Erro R, Marangi A, Bhatia K, Tinazzi M
Parkinsonism Relat Disord 2014 Aug;20(8):808-14. Epub 2014 Jun 3 doi: 10.1016/j.parkreldis.2014.05.011. PMID: 24935237
Morley JF, Pawlowski SM, Kesari A, Maina I, Pantelyat A, Duda JE
Parkinsonism Relat Disord 2014 Jul;20(7):738-42. Epub 2014 Apr 1 doi: 10.1016/j.parkreldis.2014.03.024. PMID: 24742370

Recent systematic reviews

Vizcarra JA, Lang AE, Sethi KD, Espay AJ
Mov Disord 2015 Jun;30(7):886-94. Epub 2015 May 21 doi: 10.1002/mds.26263. PMID: 25997420Free PMC Article
Caslake R, Taylor K, Scott N, Gordon J, Harris C, Wilde K, Murray A, Counsell C
Parkinsonism Relat Disord 2013 May;19(5):515-21. Epub 2013 Feb 23 doi: 10.1016/j.parkreldis.2013.01.014. PMID: 23462482
Orimo S, Suzuki M, Inaba A, Mizusawa H
Parkinsonism Relat Disord 2012 Jun;18(5):494-500. Epub 2012 Feb 8 doi: 10.1016/j.parkreldis.2012.01.009. PMID: 22321865
Dahodwala N, Siderowf A, Baumgarten M, Abrams A, Karlawish J
Parkinsonism Relat Disord 2012 Mar;18(3):216-24. Epub 2011 Sep 17 doi: 10.1016/j.parkreldis.2011.09.003. PMID: 21930414Free PMC Article
Treglia G, Cason E, Stefanelli A, Cocciolillo F, Di Giuda D, Fagioli G, Giordano A
Clin Auton Res 2012 Feb;22(1):43-55. Epub 2011 Jul 27 doi: 10.1007/s10286-011-0135-5. PMID: 21792729

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