Characteristic MRI and funduscopic findings help diagnose ARSACS outside Quebec

Gerwig, Marcus; Krüger, Stefan; Kreuz, Friedmar R.; Kreis, Stefan; Gizewski, Elke R.; Timmann, Dagmar

doi:10.1212/wnl.0b013e318200d7f8

Cited by 24 publications

(20 citation statements)

References 2 publications

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“…Most ARSACS patients show a typical triad of early-onset cerebellar ataxia, lower limb spasticity and peripheral neuropathy. Together with characteristic T2-hypointensities in the pons [2,3], these phenotypic features help to identify ARSACS in patients with unexplained ataxia. However, three mutation-proven individuals with an unusual phenotype (lacking either spasticity or peripheral neuropathy) have been described so far [1,4,5], indicating that the classical triad might not be the presenting feature in all ARSACS patients, and that ARSACS might be underdiagnosed in patients with atypical phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum

Synofzik

Soehn

Gburek‐Augustat

et al. 2013

Orphanet J Rare Dis

161

165

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BackgroundMutations in SACS, leading to autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), have been identified as a frequent cause of recessive early-onset ataxia around the world. Here we aimed to enlarge the spectrum of SACS mutations outside Quebec, to establish the pathogenicity of novel variants, and to expand the clinical and imaging phenotype.MethodsSequencing of SACS in 22 patients with unexplained early-onset ataxia, assessment of novel SACS variants in 3.500 European control chromosomes and extensive phenotypic investigations of all SACS carriers.ResultsWe identified 11 index patients harbouring 17 novel SACS variants. 9/11 patients harboured two variants of at least probable pathogenicity which were not observed in controls and, in case of missense mutations, were located in highly conserved domains. These 9 patients accounted for at least 11% (9/83) in our series of unexplained early onset ataxia subjects. While most patients (7/9) showed the classical ARSACS triad, the presenting phenotype reached from pure neuropathy (leading to the initial diagnosis of Charcot-Marie-Tooth disease) in one subject to the absence of any signs of neuropathy in another. In contrast to its name “spastic ataxia”, neither spasticity (absent in 2/9=22%) nor extensor plantar response (absent in 3/9=33%) nor cerebellar ataxia (absent in 1/9=11%) were obligate features. Autonomic features included urine urge incontinence and erectile dysfunction. Apart from the well-established MRI finding of pontine hypointensities, all patients (100%) showed hyperintensities of the lateral pons merging into the (thickened) middle cerebellar peduncles. In addition, 63% exhibited bilateral parietal cerebral atrophy, and 63% a short circumscribed thinning of the posterior midbody of the corpus callosum. In 2 further patients with differences in important clinical features, VUS class 3 variants (c.1373C>T [p.Thr458Ile] and c.2983 G>T [p.Val995Phe]) were identified. These variants were, however, also observed in controls, thus questioning their pathogenic relevance.ConclusionsWe here demonstrate that each feature of the classical ARSACS triad (cerebellar ataxia, spasticity and peripheral neuropathy) might be missing in ARSACS. Nevertheless, characteristic MRI features – which also extend to supratentorial regions and involve the cerebral cortex – will help to establish the diagnosis in most cases.

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Section: Introductionmentioning

confidence: 99%

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum

Synofzik

Soehn

Gburek‐Augustat

et al. 2013

Orphanet J Rare Dis

161

165

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“…In our opinion, some of the fundus images described as showing hypermyelinated retinal fibres are actually showing increased thickness of the RNFL as in our patients2 3 (figure 1). Therefore, we recommend that experts review these published photographs and perform a complete ophthalmological examination based on stereophotographs, RNFL photographs and analysis with digital image analysis devices.…”

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confidence: 48%

Retinal nerve fibre layer thickness in ARSACS: myelination or hypertrophy?

et al. 2012

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“…Typical MRI changes helped establishing the diagnosis in this case [15,24]. Electrophysiological findings, such as the demyelinating component of the sensorimotor peripheral neuropathy, may help distinguishing ARSACS from common recessive ataxias like Friedreich ataxia.…”

Section: Discussionmentioning

confidence: 74%

Autosomal recessive spastic ataxia of Charlevoix-Saguenay in a Portuguese child caused by a novel SACS mutation

Pimenta¹,

Costa²,

Alonso³

et al. 2017

Pediatr Dimensions

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Introduction: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disease characterized by cerebellar ataxia, peripheral neuropathy and pyramidal tract signs. Since its first report from Québec, more than 100 disease-causing variants have been reported in ARSACS, with variable clinical presentation. MRI imaging may help establishing the clinical diagnosis, especially if typical changes are present.

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Characteristic MRI and funduscopic findings help diagnose ARSACS outside Quebec

Cited by 24 publications

References 2 publications

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum

Retinal nerve fibre layer thickness in ARSACS: myelination or hypertrophy?

Autosomal recessive spastic ataxia of Charlevoix-Saguenay in a Portuguese child caused by a novel SACS mutation

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