Establishing diagnostic criteria for Perry syndrome

Mishima, Takayasu; Fujioka, Shinsuke; Tomiyama, Hiroyuki; Yabe, Ichiro; Kurisaki, Ryoichi; Fujii, Naoki; Neshige, Ryuji; Ross, Owen A.; Farrer, Matthew J.; Dickson, Dennis W.; Wszołek, Zbigniew K.; Tsuboi, Yoshio

doi:10.1136/jnnp-2017-316864

Cited by 43 publications

(78 citation statements)

References 38 publications

(73 reference statements)

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“…However, Patient 1 with distal motor neuropathy had an extremely early age of onset as well as congenital foot deformity, in comparison with all other DCTN1‐related cases reported before. Interestingly, DCNT1 mutation can also lead to Perry syndrome, which is characterized by rapidly progressive parkinsonism accompanied by depression/apathy, unintentional weight loss and respiratory failure . Patients usually show levodopa‐resistant/responsive resting tremor, rigidity, bradykinesia, postural instability and autonomic dysfunction, and reminiscent of Parkinson’s disease.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, Perry syndrome can be easily misdiagnosed as Parkinson’s disease, especially during early stage. The major death cause is central hypoventilation or pneumonia . The clinical characterizations of DCNT1‐related spectrum are summarized in Table .…”

Section: Discussionmentioning

confidence: 99%

“…The major death cause is central hypoventilation or pneumonia. 8,[15][16][17][18] The clinical characterizations of DCNT1-related spectrum are summarized in Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…Different phenotypes are mainly characterized as involvement of inferior motor neurons or superior motor neurons or both, with different ages of onset and various progress speed. DCTN1 ‐related dHMN, also known as dHNM type 7B, presents with distal limb dystrophy and weakness appearing at early adulthood, whereas Perry syndrome is characterized by middle‐age‐onset parkinsonism, depression, weight loss, and central hypoventilation . Recently, frontotemporal dementia (FTD) has also been considered as one of the phenotypes, indicating the DCTN1 ‐related spectrum is still expanding.…”

Section: Introductionmentioning

confidence: 99%

“…DCTN1-related dHMN, also known as dHNM type 7B, presents with distal limb dystrophy and weakness appearing at early adulthood, 6 whereas Perry syndrome is characterized by middle-age-onset parkinsonism, depression, weight loss, and central hypoventilation. 4,7,8 Recently, frontotemporal dementia (FTD) has also been considered as one of the phenotypes, 9 indicating the DCTN1-related spectrum is still expanding. Since the year of 2003, DCTN1 mutation was first associated with human disease, 6 more than 20 variations have been reported in sporadic or familial cases.…”

Section: Introductionmentioning

confidence: 99%

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New phenotype of DCTN1‐related spectrum: early‐onset dHMN plus congenital foot deformity

Tian

Liu

Zhou

et al. 2020

Ann Clin Transl Neurol

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Objective To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype–genotype relationship. Methods Patient 1 is a 23‐year‐old man with congenital foot deformity and life‐long distal muscle weakness and atrophy. Patient 2 is a 48‐year‐old woman with adult‐onset progressive weakness, lower limbs atrophy, and pyramid bundle signs. Electrophysiology test showed normal nerve conduction velocity of both patients and neurogenic changes in needle electromyography. Open sural nerve biopsy for Patient 1 showed slight loss of myelinated nerve fibers. Both patients were performed with whole‐exome sequencing followed by functional study of identified variants. Results Two mutations in DCTN1 gene were identified in Patient 1 (c.626dupC) and Patient 2 (c.3823C>T), respectively. In vitro, the wild type mostly located in cytoplasm and colocalized with α‐tubulin. However, c.626dupC tended to be trapped into nuclear and the c.3823C>T formed cytoplasmic aggregates, both losing colocalization with α‐tubulin. Western blotting showed a truncated mutant with less molecular weight of c.626dupC was expressed. Interpretation We identify two novel DCTN1 mutations causing different phenotypes: (1) early‐onset distal hereditary motor neuropathy plus congenital foot malformation and (2) amyotrophic lateral sclerosis, respectively. We provide the initial evidence that foot developmental deficiency probably arises from subcellular localizing abnormality of Dynactin 1, revealing DCTN1‐related spectrum is still expanding.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The major death cause is central hypoventilation or pneumonia. 8,[15][16][17][18] The clinical characterizations of DCNT1-related spectrum are summarized in Table 1.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

New phenotype of DCTN1‐related spectrum: early‐onset dHMN plus congenital foot deformity

Tian

Liu

Zhou

et al. 2020

Ann Clin Transl Neurol

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Neuropathology of Perry Syndrome: Evidence of Medullary and Hypothalamic Involvement

Kim

Alghefari

Jenkins

et al. 2021

Movement Disord Clin Pract

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BackgroundBackground: Perry syndrome is a rare genetic parkinsonian disorder with TAR DNA binding protein 43 (TDP-43) pathology clinically presenting with parkinsonism, neuropsychiatric features, weight loss, and central hypoventilation. As respiratory complications are often the cause of death, studies likely show the early stage of the neurodegenerative process. Because of the rarity of this condition, few studies exist, and each case provides insight into pathological findings in this neurodegenerative condition. Objective Objective: To study the clinical and pathological correlations of an autopsy case of Perry syndrome. Methods Methods: The patient was a woman in her 50s with Perry syndrome and a DCTN1 gene mutation. Between October 2016 and July 2019, she underwent postmortem and pathological examination at University Hospital in London, Ontario, Canada. Data were obtained through clinical pathological examination. Results Results: Microscopy showed significant neuronal loss with pigmentary incontinence and gliosis in the substantia nigra. There was no atrophy elsewhere, including the frontal and cingulate cortex. Intraneuronal cytoplasmic TDP-43 inclusions and neurites were noticed in a moderate number in the substantia nigra and midbrain and were sparsely noticed in the basal ganglia, thalamus, thoracic motor neuron, posterior nucleus of the hypothalamus, and rostral ventral medulla. β-Amyloid, Lewy body, and tau pathologies were absent. Rare axonal swelling was identified at the rostral ventrolateral medulla. Conclusions and RelevanceConclusions and Relevance: This study confirms that Perry syndrome is characterized by TDP-43 pathology with absent Lewy bodies or tau pathology. These findings support the hypothesis of dysfunctional neurons in the medulla and hypothalamus, which may respectively correlate to the clinical symptoms of hypoventilation and weight loss in Perry syndrome.Perry syndrome (PS) is a rare neurodegenerative disorder with parkinsonism, neuropsychiatric features (depression/apathy), weight loss, and central hypoventilation leading to respiratory failure. 1 The causative gene is an autosomal-dominant pathogenic variant in DCTN1, which encodes dynactin subunit p150 Glued involved in axonal transport. 2 Because of the rarity of the condition, few pathological studies exist. However, it is a unique parkinsonian disorder characterized by the presence of TAR DNA binding protein 43 (TDP-43) pathology in previous studies, especially in the substantia nigra (SN). 3 Despite profound respiratory failure and weight loss in this disorder, there is no clear consensus on the clinicopathologic correlation of these symptoms. PS has been described in at least 18 families worldwide, 2,4 and we provide a pathologic study of a patient in a newly identified family to better understand the pathologic findings in PS. MethodsAt autopsy the brain was retrieved and then fixed in 10% neutral formalin for 2 weeks. After fixation, formalin-fixed paraffin embedded blocks were prepared. Blocks from the bilateral

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Perry Syndrome with Intrafamilial Heterogeneity in Presentation and Survival Including Acute Respiratory Failure: Case Series

Boardman

Ponte

Chaouch

et al. 2022

Movement Disord Clin Pract

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Background Perry syndrome is a rare autosomal dominant parkinsonian disorder characterized by respiratory failure. The variability in respiratory presentation in this condition is incompletely understood. Cases We report 2 first‐degree relatives with Perry syndrome attributed to the same mutation in the Dynactin 1 (DCTN1) gene. Their clinical presentations with respect to parkinsonism and respiratory failure were heterogeneous. The proband presented with acute respiratory failure requiring invasive ventilation on a background of parkinsonism and remains alive more than 3 years later with a good levodopa response. We contrast this with the published literature, in which acute respiratory presentations were associated with a poor outcome. The proband's brother presented with parkinsonism together with early falls and gait impairment and died following gradual hypoventilation despite noninvasive respiratory support. Conclusions Perry syndrome can show intrafamily heterogeneity in both movement disorder and respiratory presentations. Acute respiratory failure is often but not always associated with a poor outcome.

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Establishing diagnostic criteria for Perry syndrome

Cited by 43 publications

References 38 publications

New phenotype of DCTN1‐related spectrum: early‐onset dHMN plus congenital foot deformity

New phenotype of DCTN1‐related spectrum: early‐onset dHMN plus congenital foot deformity

Neuropathology of Perry Syndrome: Evidence of Medullary and Hypothalamic Involvement

Perry Syndrome with Intrafamilial Heterogeneity in Presentation and Survival Including Acute Respiratory Failure: Case Series

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