Palpebral ptosis as the initial symptom of amyotrophic lateral sclerosis

Shindo, Kazumasa; Satake, Akane; Fukao, Toko; Ichinose, Yuichi; Takiyama, Yoshihisa

doi:10.1007/s10072-019-04030-y

Cited by 3 publications

(3 citation statements)

References 5 publications

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“…Ocular ptosis is not a classic symptom of ALS, although it has been rarely reported ( Pinto and de Carvalho, 2008 ; De Marchi et al, 2018 ; Shindo et al, 2020 ). Intriguingly, De Marchi et al reported two siblings with a history of progressive ptosis without ocular movement impairment, diagnosed with a bulbar ALS with rapid progression ( De Marchi et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, ALS' pathogenesis is considered as a multi-step disease process, where multiple hits, both genetic and environmental, are needed to develop the disease (Al-Chalabi et al, 2014). Furthermore, several observations proved that the burden of multiple genetic rare variants might trigger the degenerative process, modulating also the clinical phenotype (van Blitterswijk et al, 2012). Recently, a large study on ALS (van Rheenen et al, 2021) pointed to the burden of multiple risk factors disclosed in the nuclear genome but missed to consider the possible impact of mitochondrial DNA (mtDNA) variation, which is frequently neglected but may contribute to the pathogenesis or modulate the phenotype also in ALS.…”

Section: Introductionmentioning

confidence: 99%

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The genetic puzzle of a SOD1-patient with ocular ptosis and a motor neuron disease: a case report

Vacchiano,

Palombo,

Ormanbekova

et al. 2023

Front. Genet.

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with atypical clinical features consisting in progressive ocular ptosis and sensorineural deafness. Genetic analyses revealed two heterozygous variants, in the SOD1 (OMIM*147450) and the TBK1 (OMIM*604834) genes respectively, and furthermore mitochondrial DNA (mtDNA) sequencing identified the homoplasmic m.14484T>C variant usually associated with Leber’s Hereditary Optic Neuropathy (LHON). We discuss how all these variants may synergically impinge on mitochondrial function, possibly contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, shaping the clinical ALS phenotype enriched by adjunctive clinical features.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The genetic puzzle of a SOD1-patient with ocular ptosis and a motor neuron disease: a case report

Vacchiano,

Palombo,

Ormanbekova

et al. 2023

Front. Genet.

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show abstract

“…Ocular ptosis is not a classic symptom of ALS, although it has been rarely reported [10][11][12]. Intriguingly, De Marchi et al reported two siblings with a history of progressive ptosis without ocular movement impairment, diagnosed with a bulbar ALS with rapid progression [12].…”

Section: Discussionmentioning

confidence: 99%

The Genetic Puzzle of a SOD1-Patient with Ocular Ptosis and a Motor Neuron Disease: How Many Variants Contribute to the Phenotype?

Vacchiano¹,

Palombo²,

Ormanbekova³

et al. 2023

Preprint

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with an atypical phenotype, due to the presence of a progressive ocular ptosis. Genetic analyses revealed two variants in SOD1 and TBK1 genes respectively and the LHON-associated m.14484T>C variant in the mitochondrial DNA (mtDNA). We discuss how all these variants may synergically impinge on mitochondrial function, contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, possibly influencing the clinical ALS phenotype.

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