Multiple System Atrophy and Amyotrophic Lateral Sclerosis in a Family With Hexanucleotide Repeat Expansions in<i>C9orf72</i>

Goldman, Jill; Quinzii, Catarina M.; Dunning-Broadbent, Jane; Waters, Cheryl; Mitsumoto, Hiroshi; Brannagan, Thomas H.; Cosentino, Stephanie; Huey, Edward D.; Nagy, Péter L.; Kuo, Sheng‐Han

doi:10.1001/jamaneurol.2013.5762

Cited by 67 publications

(60 citation statements)

References 18 publications

(26 reference statements)

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“…One notorious exception with predominant temporal atrophy is represented by C9orf72-related cases with primary progressive aphasia phenotype 58 . The finding of hot-cross bun sign in the pons has also been described in the context of C9orf72-spectrum in a single case of late-onset cerebellar variant of multiple system atrophylike phenotype 49 .…”

Section: Neuroimaging Studiesmentioning

confidence: 68%

“…It is also documented the predisposition of some populations to parkinsonism in cases of C9orf72 repeat expansion 12 . Atypical parkinsonism with cerebellar ataxia mimicking multiple system atrophy has also been described 49 , the same way as cerebellar ataxia with retained reflexes 50 and isolated olivopontocerebellar atrophy with hot-cross bun sign in the pons 26,51 . Due to its exceptionality, cerebellar ataxia as a clinical manifestations of C9orf72 expansion should be suspected only in cases with proper familial dementia or especially with motor neuron disease.…”

Section: Clinical and Laboratory Characterizationmentioning

confidence: 92%

“…UBQLN2 gene mutations are great mimickers frequently differentiated in clinical means by the absence of psychiatric features (not behavioural symptoms) and lower motor neuron involvement 14 . In cases with pleiotropic heterogeneous phenotypic variability of repeat expansions, association with previously described pathogenic mutations in GRN or MAPT genes must be done 49 .…”

Section: Clinical and Laboratory Characterizationmentioning

confidence: 99%

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C9orf72-related disorders: expanding the clinical and genetic spectrum of neurodegenerative diseases

Souza

Pinto

Oliveira

2015

Arq. Neuro-Psiquiatr.

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Neurodegenerative diseases represent a heterogeneous group of neurological conditions primarily involving dementia, motor neuron disease and movement disorders. They are mostly related to different pathophysiological processes, notably in family forms in which the clinical and genetic heterogeneity are lush. In the last decade, much knowledge has been acumulated about the genetics of neurodegenerative diseases, making it essential in cases of motor neuron disease and frontotemporal dementia the repeat expansions of C9orf72 gene. This review analyzes the main clinical, radiological and genetic aspects of the phenotypes related to the hexanucleotide repeat expansions (GGGGCC) of C9orf72 gene. Future studies will aim to further characterize the neuropsychological, imaging and pathological aspects of the extra-motor features of motor neuron disease, and will help to provide a new classification system that is both clinically and biologically relevant.Keywords: neurodegenerative diseases, motor neuron disease, frontotemporal dementia, parkinsonism, C9orf72. RESUMOAs doenças neurodegenerativas representam um grupo heterogêneo de condições neurológicas envolvendo fundamentalmente síndromes demenciais, doenças do neurônio motor e distúrbios de movimento. Relacionam-se, em sua maioria, a processos fisiopatológicos distintos, destacadamente nas formas familiares em que a heterogeneidade clínica e genética são exuberantes. Na última década, muito conhecimento se acumulou a respeito da genética das doenças neurodegenerativas, tornando-se bastante importante nos casos de doenças do neurônio motor e de demência frontotemporal as expansões de repetições do gene C9orf72. Esta revisão aborda os principais aspectos clínicos, radiológicos e genéticos relativos aos fenótipos relacionados à expansão de repetição do hexanucleotídeo (GGGGCC) no gene C9orf72. Estudos futuros vão objetivar a caracterização dos aspectos neuropsicológicos, de imagem e patológicos dos achados extra-motores da doença do neurônio motor e ajudarão a fornecer um novo sistema de classificação relevante em termos clínicos e biológicos.Palavras-chave: doenças neurodegenerativas, doença do neurônio motor, demência frontotemporal, parkinsonismo, C9orf72.

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Section: Neuroimaging Studiesmentioning

confidence: 68%

Section: Clinical and Laboratory Characterizationmentioning

confidence: 92%

Section: Clinical and Laboratory Characterizationmentioning

confidence: 99%

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C9orf72-related disorders: expanding the clinical and genetic spectrum of neurodegenerative diseases

Souza

Pinto

Oliveira

2015

Arq. Neuro-Psiquiatr.

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“…There is also a report of clinically diagnosed MSA with C9orf72 expansion in a family with ALS. 34 Though C9orf72 expansions are associated with parkinsonian symptoms and syndromes, this is the only report of suspected MSA with C9orf72. Subsequent studies, including a series of 100 pathologically confirmed MSA cases, 35 have failed to produce a link between this expansion and MSA.…”

Section: Other Implicated Genesmentioning

confidence: 80%

Understanding Multiple System Atrophy—Could Genetics Lead the Way?

Sklerov¹,

Waters²

2016

US Neurology

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Multiple system atrophy (MSA) is a progressive, adult-onset, neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia, autonomic failure, and corticospinal tract dysfunction. It is considered a rare disease, similar in frequency to the more well-known neurodegenerative disease amyotrophic lateral sclerosis or Lou Gehrig’s disease. Though MSA has not traditionally been considered a genetic disease, new evidence is emerging supporting some genetic predisposition in many patients. In this short review, we will discuss advances in the knowledge of genetics in MSA and how this has furthered our understanding of the pathophysiology of the disease. There is still much unknown about this disease, but some of the recent advances made in MSA genetics may give important clues to understanding the pathogenesis and treatment of this disease.

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“…23,24 The C9orf72 HRE also represents the most common genetic cause of frontotemporal dementia (FTD), which is characterized by degeneration of the frontal and temporal lobes of the brain and is the second most common type of dementia in people younger than 65. 25 Furthermore, the C9orf72 HRE is linked to rare cases of other neurological conditions, including Alzheimer's disease, [26][27][28][29] Huntington's disease, 30 multiple system atrophy, 31 depressive pseudodementia, 32 bipolar disorder, [33][34][35] and schizophrenia. 36 Given these wide-ranging implications, understanding the molecular mechanisms of C9orf72 HRE-associated diseases has become a significant challenge in the study of neurodegeneration.…”

Section: C9orf72 Repeat Expansion Diseasesmentioning

confidence: 99%