MedGen

Parkin type of early-onset Parkinson disease (PARK-Parkin) is characterized by the cardinal signs of Parkinson disease (PD): bradykinesia, resting tremor, and rigidity. The median age at onset is 31 years (range: 3-81 years). The disease is slowly progressive: disease duration of more than 50 years has been reported. Clinical findings vary; hyperreflexia is common. Lower-limb dystonia may be a presenting sign and cognitive decline appears to be no more frequent than in the general population. Dyskinesia as a result of treatment with levodopa frequently occurs. [from GeneReviews]

LRRK2 Parkinson disease (PD) is characterized by features consistent with idiopathic PD: initial motor features of slowly progressive asymmetric tremor at rest and/or bradykinesia, cogwheel muscle rigidity, postural instability, and gait abnormalities that may include festination and freezing. Certain nonmotor symptoms in LRRK2-PD, especially REM sleep behavior disorder and cognitive decline, may occur at similar or slightly reduced frequency compared to typical idiopathic* PD. Onset is generally after age 50, although early-onset (in the 20s) and late-onset (in the 90s) disease has been described. * Idiopathic PD refers to the presence of signs and symptoms of PD for which the etiology is currently unknown and in which there is no known family history of PD. [from GeneReviews]

Kufor-Rakeb syndrome is a rare autosomal recessive form of juvenile-onset atypical Parkinson disease (PARK9) associated with supranuclear gaze palsy, spasticity, and dementia. Some patients have neuroradiologic evidence of iron deposition in the basal ganglia, indicating that the pathogenesis of PARK9 can be considered among the syndromes of neurodegeneration with brain iron accumulation (NBIA; see 234200) (summary by Bruggemann et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600. Biallelic mutation in the ATP13A2 gene also causes autosomal recessive spastic paraplegia-78 (SPG78; 617225), an adult-onset neurodegenerative disorder with overlapping features. Patients with SPG78 have later onset and prominent spasticity, but rarely parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017). [from OMIM]

PINK1 type of young-onset Parkinson disease is characterized by early onset (mean age 33 years) of tremor, bradykinesia, and rigidity that are often indistinguishable from other causes of Parkinson disease. Lower-limb dystonia may be a presenting sign. Postural instability, hyperreflexia, abnormal behavior, and psychiatric manifestations have been described. The disease is usually slowly progressive. Individuals have a marked and sustained response to oral administration of levodopa (L-dopa), frequently associated with L-dopa-induced fluctuations and dyskinesias. [from GeneReviews]

Parkinson disease is the second most common neurogenic disorder after Alzheimer disease (AD; 104300), affecting approximately 1% of the population over age 50. Clinical manifestations include resting tremor, muscular rigidity, bradykinesia, and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia (Polymeropoulos et al., 1996). For a general phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see 168600. [from OMIM]

Parkinson disease (PD) was first described by James Parkinson in 1817. It is the second most common neurodegenerative disorder after Alzheimer disease (AD; 104300), affecting approximately 1% of the population over age 50 (Polymeropoulos et al., 1996). Reviews Warner and Schapira (2003) reviewed the genetic and environmental causes of Parkinson disease. Feany (2004) reviewed the genetics of Parkinson disease and provided a speculative model of interactions among proteins implicated in PD. Lees et al. (2009) provided a review of Parkinson disease, with emphasis on diagnosis, neuropathology, and treatment. Genetic Heterogeneity of Parkinson Disease Several loci for autosomal dominant Parkinson disease have been identified, including PARK1 (168601) and PARK4, caused by mutation in or triplication of the alpha-synuclein gene (SNCA; 163890), respectively, on 4q22; PARK5 (191342), caused by mutation in the UCHL1 gene on 4p13; PARK8 (607060), caused by mutation in the LRRK2 gene (609007) on 12q12; PARK11 (607688), caused by mutation in the GIGYF2 gene (612003) on 2q37; PARK13 (610297), caused by mutation in the HTRA2 gene (606441) on 2p13; PARK17 (614203), caused by mutation in the VPS35 gene (601501) on 16q11; PARK18 (614251), caused by mutation in the EIF4G1 gene (600495) on 3q27; PARK22 (616710), caused by mutation in the CHCHD2 gene (616244) on 7p11; and PARK24 (619491), caused by mutation in the PSAP gene (176801) on 10q22. Several loci for autosomal recessive early-onset Parkinson disease have been identified: PARK2 (600116), caused by mutation in the gene encoding parkin (PRKN, PARK2; 602544) on 6q26; PARK6 (605909), caused by mutation in the PINK1 gene (608309) on 1p36; PARK7 (606324), caused by mutation in the DJ1 gene (PARK7; 602533) on 1p36; PARK14 (612953), caused by mutation in the PLA2G6 gene (603604) on 22q13; PARK15 (260300), caused by mutation in the FBXO7 gene (605648) on 22q12-q13; PARK19A (615528) and PARK19B (see 615528), caused by mutation in the DNAJC6 gene (608375) on 1p32; PARK20 (615530), caused by mutation in the SYNJ1 gene (604297) on 21q22; and PARK23 (616840), caused by mutation in the VPS13C gene (608879) on 15q22; and PARK25 (620482), caused by mutation in the PTPA gene (600756) on 9q34. PARK3 (602404) has been mapped to chromosome 2p13; PARK10 (606852) has been mapped to chromosome 1p34-p32; PARK16 (613164) has been mapped to chromosome 1q32. See also PARK21 (616361). A locus on the X chromosome has been identified (PARK12; 300557). There is also evidence that mitochondrial mutations may cause or contribute to Parkinson disease (see 556500). Susceptibility to the development of the more common late-onset form of Parkinson disease has been associated with polymorphisms or mutations in several genes, including GBA (606463), MAPT (157140), MC1R (155555), ADH1C (103730), and genes at the HLA locus (see, e.g., HLA-DRA, 142860). Each of these risk factors independently may have a modest effect on disease development, but together may have a substantial cumulative effect (Hamza et al., 2010). Susceptibility to PD may also be conferred by expanded trinucleotide repeats in several genes causing other neurologic disorders usually characterized by spinocerebellar ataxia (SCA), including the ATXN2 (601517), ATXN3 (607047), TBP (600075), and ATXN8OS (603680) genes. [from OMIM]

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.

Parkinson'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.

Often 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.

Parkinson'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. [from MedlinePlus Genetics]

Ovarian cancer, the leading cause of death from gynecologic malignancy, is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases (Chi et al., 2001). These typical features relate to the biology of the disease, which is a principal determinant of outcome (Auersperg et al., 2001). Epithelial ovarian cancer is the most common form and encompasses 5 major histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Epithelial ovarian cancer arises as a result of genetic alterations sustained by the ovarian surface epithelium (Stany et al., 2008; Soslow, 2008). [from OMIM]

VPS35-related Parkinson disease (VPS35-PD) is defined as Parkinson disease caused by heterozygous VPS35 pathogenic variants. Currently, the only known VPS35 variant with confirmed pathogenicity is c.1858G>A (p.Asp620Asn). Except for a younger age of onset, VPS35-PD is clinically indistinguishable from Parkinson disease of unknown cause (so-called sporadic Parkinson disease). Variability among 50 individuals reported with molecularly confirmed VPS35-PD includes age of onset (mean: 51.0±8.7 years; range: 34-68 years), Parkinson subtype (tremor, akinetic rigid, mixed), first motor symptom, course of the disease (unilateral onset and slow disease progression are typical; dyskinesia and motor fluctuations may occur), and presence/absence of neuropsychiatric manifestations (including depression, schizophrenia, learning difficulties, mild cognitive impairment, and dementia). [from GeneReviews]

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. [from OMIM]

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.

Parkinson'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.

Often 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.

Parkinson'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. [from MedlinePlus Genetics]

Parkinson'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.

Often 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.

Parkinson'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.

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. [from MedlinePlus Genetics]

Parkinson'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.

Often 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.

Parkinson'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.

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. [from MedlinePlus Genetics]

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.

Parkinson'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.

Often 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.

Parkinson'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. [from MedlinePlus Genetics]

Parkinson'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.

Often 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.

Parkinson'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.

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. [from MedlinePlus Genetics]

Parkinson'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.

Often 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.

Parkinson'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.

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. [from MedlinePlus Genetics]

DNAJC6 Parkinson disease is a complex early-onset neurologic disorder whose core features are typical parkinsonian symptoms including bradykinesia, resting tremor, rigidity, and postural instability. The majority of individuals have juvenile onset and develop symptoms before age 21 years. Developmental delay, intellectual disability, seizures, other movement disorders (e.g., dystonia, spasticity, myoclonus), and neuropsychiatric features occur in the majority of individuals with juvenile onset and often precede parkinsonism. The onset of parkinsonian features usually occurs toward the end of the first or beginning of the second decade and the disease course is rapidly progressive with loss of ambulation in mid-adolescence in the majority of individuals. Additional features include gastrointestinal manifestations and bulbar dysfunction. A minority of individuals with DNAJC6 Parkinson disease develop early-onset parkinsonism with symptom onset in the third to fourth decade and absence of additional neurologic features. [from GeneReviews]

Parkinson'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.

Often 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.

Parkinson'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.

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. [from MedlinePlus Genetics]

Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (see 256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency resulting from mutation in nuclear-encoded genes include MC1DN1, caused by mutation in the NDUFS4 gene (602694); MC1DN2 (618222), caused by mutation in the NDUFS8 gene (602141); MC1DN3 (618224), caused by mutation in the NDUFS7 gene (601825); MC1DN4 (618225), caused by mutation in the NDUFV1 gene (161015); MC1DN5 (618226), caused by mutation in the NDUFS1 gene (157655); MC1DN6 (618228), caused by mutation in the NDUFS2 gene (602985); MC1DN7 (618229), caused by mutation in the NDUFV2 gene (600532); MC1DN8 (618230), caused by mutation in the NDUFS3 gene (603846); MC1DN9 (618232), caused by mutation in the NDUFS6 gene (603848); MC1DN10 (618233), caused by mutation in the NDUFAF2 gene (609653); MC1DN11 (618234), caused by mutation in the NDUFAF1 gene (606934); MC1DN12 (301020), caused by mutation in the NDUFA1 gene (300078); MC1DN13 (618235), caused by mutation in the NDUFA2 gene (602137); MC1DN14 (618236), caused by mutation in the NDUFA11 gene (612638); MC1DN15 (618237), caused by mutation in the NDUFAF4 gene (611776); MC1DN16 (618238), caused by mutation in the NDUFAF5 gene (612360); MC1DN17 (618239), caused by mutation in the NDUFAF6 gene (612392); MC1DN18 (618240), caused by mutation in the NDUFAF3 gene (612911); MC1DN19 (618241), caused by mutation in the FOXRED1 gene (613622); MC1DN20 (611126), caused by mutation in the ACAD9 gene (611103); MC1DN21 (618242), caused by mutation in the NUBPL gene (613621); MC1DN22 (618243), caused by mutation in the NDUFA10 gene (603835); MC1DN23 (618244), caused by mutation in the NDUFA12 gene (614530); MC1DN24 (618245), caused by mutation in the NDUFB9 gene (601445); MC1DN25 (618246), caused by mutation in the NDUFB3 gene (603839); MC1DN26 (618247), caused by mutation in the NDUFA9 gene (603834); MC1DN27 (618248), caused by mutation in the MTFMT gene (611766); MC1DN28 (618249), caused by mutation in the NDUFA13 gene (609435); MC1DN29 (618250), caused by mutation in the TMEM126B gene (615533); MC1DN30 (301021), caused by mutation in the NDUFB11 gene (300403); MC1DN31 (618251), caused by mutation in the TIMMDC1 gene (615534); MC1DN32 (618252), caused by mutation in the NDUFB8 gene (602140); MC1DN33 (618253), caused by mutation in the NDUFA6 gene (602138); MC1DN34 (618776), caused by mutation in the NDUFAF8 gene (618461); MC1DN35 (619003), caused by mutation in the NDUFB10 gene (603843); MC1DN36 (619170), caused by mutation in the NDUFC2 gene (603845); MC1DN37 (619272), caused by mutation in the NDUFA8 gene (603359); MC1DN38 (619382), caused by mutation in the DNAJC30 gene (618202); and MC1DN39 (620135), caused by mutation in the NDUFB7 gene (603842). Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome. Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085). [from OMIM]