Genetic mimics of the non-genetic atypical parkinsonian disorders – the ‘atypical’ atypical

Giagkou, Nikolaos; Bhatia, Kailash P.; Höglinger, Günter U.; Stamelou, María

doi:10.1016/bs.irn.2019.10.008

Cited by 10 publications

(15 citation statements)

References 226 publications

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“…The contribution of genetic factors to atypical parkinsonian syndromes is increasingly recognized (Scholz & Bras, 2015). In parallel, there is a growing body of evidence on new genetic conditions presenting with features of APS, called “atypical” atypical parkinsonism (Giagkou et al., 2019; Stamelou et al., 2013). To establish whether these familial cases of APS are “true” APS or AP‐look‐alikes would require further genetic and pathological investigations.…”

Section: Discussionmentioning

confidence: 99%

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Atypical parkinsonian syndromes in a North African tertiary referral center

et al. 2020

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Introduction Data on epidemiology of atypical parkinsonian syndromes (APS) in North African countries are limited. Our objective was to study the epidemiological features of APS in a Tunisian population. Methods We conducted a 17‐year retrospective cross‐sectional descriptive study in the Department of Neurology at Razi University Hospital. We included all patients responding to consensus diagnosis criteria of APS. We recorded demographic and clinical data. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction. Results We included 464 APS patients. Hospital prevalence of APS among all parkinsonism cases was 20.6%. Mean annual increase of incidence defined as newly diagnosed APS cases per year reached 38.8%/year. APS were divided into 4 etiological subgroups: dementia with Lewy bodies (DLB; 56.7%); progressive supranuclear palsy(PSP; 16.2%); multiple system atrophy (MSA; 14.6%); and finally corticobasal syndrome (CBS; 12.5%). Sex‐ratio was 1.2. This male predominance was found in all subgroups except MSA ( p = .013). Mean age at onset was 68.5 years, most belated in DLB (69.7 years; p < .001). Young‐onset parkinsonism (<40 years) was found only in MSA subgroup ( p = .031). Parkinsonism was of late onset (>70 years) in 50.7% of patients and was significantly associated with DLB subgroup ( p = .013). Inaugural parkinsonism was associated with CBS and MSA ( p = .0497), and gait disorders at disease onset were associated with PSP and MSA ( p = .0062). Cognitive and mood disorders were more marked in DLB and most preserved in MSA. Consanguinity was more marked in CBS ( p = .037), and family history of dementia and psychiatric diseases was more common in DLB. Thirty‐seven families with similar cases of APS were identified. Conclusions This is the largest African epidemiological study on APS. In our population, APS were frequent and dominated by DLB. The age of onset of parkinsonism was the most decisive feature for differential diagnosis.

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Section: Discussionmentioning

confidence: 99%

“…In fact, in a study (Scholz & Bras, 2015). In parallel, there is a growing body of evidence on new genetic conditions presenting with features of APS, called "atypical" atypical parkinsonism (Giagkou et al, 2019;Stamelou et al, 2013).…”

Section: Ta B L E 1 Patient's Characteristicsmentioning

confidence: 99%

Atypical parkinsonian syndromes in a North African tertiary referral center

et al. 2020

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“…[18][19][20] The later age at onset and the frontal features caused by DCTN1 mutations are shared by patients with other mutations in genes implicated in frontotemporal dementia/parkinsonism, such as GRN and C9ORF72. 21 In addition, weight loss and hypoventilation present in patients with DCTN1 mutations are typically also found in patients with stiffness or atypical parkinsonism because of DPPX and IGLON5 antibodies, respectively. [22][23][24] When comparing clinically typical dominant (PARK-SNCA, PARK-LRRK2, PARK-VPS35) 1 and recessive forms and is highest in patients with nonmonogenic atypical parkinsonism (64 years).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to genetic testing, they are typically revealed through clinical and imaging clues 18‐20 . The later age at onset and the frontal features caused by DCTN1 mutations are shared by patients with other mutations in genes implicated in frontotemporal dementia/parkinsonism, such as GRN and C9ORF72 21 . In addition, weight loss and hypoventilation present in patients with DCTN1 mutations are typically also found in patients with stiffness or atypical parkinsonism because of DPPX and IGLON5 antibodies, respectively 22‐24 …”

Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review

et al. 2021

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A BS TRACT: This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95% CI, 86.3%-86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10 −12 ) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57-70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms

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“…On top of this, vertical gaze palsy can be seen in a lot of other disorders apart from PSP-RS and asymmetric dystonic stiff limb presentation can be seen in other disorders besides CBS. Thus, clinicians should always be aware of these look-alikes (“mimics”) of PSP and CBS ( 45 , 46 ) ( Table 2 ).…”

Section: Classification Of Tauopathies—current Status and Pitfallsmentioning

confidence: 99%

Tauopathy and Movement Disorders—Unveiling the Chameleons and Mimics

Ganguly

Jog

2020

Front. Neurol.

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The spectrum of tauopathy encompasses heterogenous group of neurodegenerative disorders characterized by neural or glial deposition of pathological protein tau. Clinically they can present as cognitive syndromes, movement disorders, motor neuron disease, or mixed. The heterogeneity in clinical presentation, genetic background, and underlying pathology make it difficult to classify and clinically approach tauopathy. In the literature, tauopathies are thus mostly highlighted from pathological perspective. From clinical standpoint, cognitive syndromes are often been focussed while reviewing tauopathies. However, the spectrum of tauopathy has also evolved significantly in the domain of movement disorders and has transgressed beyond the domain of primary tauopathies. Secondary tauopathies from neuroinflammation or autoimmune insults and some other "novel" tauopathies are increasingly being reported in the current literature, while some of them are geographically isolated. Because of the overlapping clinical phenotypes, it often becomes difficult for the clinician to diagnose them clinically and have to wait for the pathological confirmation by autopsy. However, each of these tauopathies has some clinical and radiological signatures those can help in clinical diagnosis and targeted genetic testing. In this review, we have exposed the heterogeneity of tauopathy from a movement disorder perspective and have provided a clinical approach to diagnose them ante mortem before confirmatory autopsy. Additionally, phenotypic variability of these disorders (chameleons) and the look-alikes (mimics) have been discussed with potential clinical pointers for each of them. The review provides a framework within which new and as yet undiscovered entities can be classified in the future.

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Genetic mimics of the non-genetic atypical parkinsonian disorders – the ‘atypical’ atypical

Cited by 10 publications

References 226 publications

Atypical parkinsonian syndromes in a North African tertiary referral center

Atypical parkinsonian syndromes in a North African tertiary referral center

Genotype–Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review

Tauopathy and Movement Disorders—Unveiling the Chameleons and Mimics

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