Atypical late-onset hereditary spastic paraplegia with thin corpus callosum due to novel compound heterozygous mutations in the SPG11 gene

Abstract Background SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. Methods In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. Results By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language. Conclusions The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.

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Mild Cognitive Impairment in novel SPG11 Mutation-Related Sporadic Hereditary Spastic Paraplegia with Thin Corpus Callosum

10.21203/rs.3.rs-60928/v1 ◽

2020 ◽

Author(s):

Chuan Li ◽

Qi Yan ◽

Feng-ju Duan ◽

Chao Zhao ◽

Zhuo Zhang ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Corpus Callosum ◽

Hereditary Spastic Paraplegia ◽

Late Onset ◽

Spastic Paraplegia ◽

Thin Corpus Callosum ◽

Modeling Analysis ◽

Sporadic Cases ◽

Multiple Domains

Abstract Background: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are still lots of sporadic late-onset HSP-TCC cases with negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. Methods: In this study, we performed next generation sequencing in four sporadic late-onset patients with spastic paraplegia and thin corpus callosum (TCC), and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. Results: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (<26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of visuoexecutive function, delayed recall, abstraction and language correlated with prefrontal deficits.Conclusions: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI characterized with dysfunction of prefrontal lobe in SPG11-related HSP-TCC, which should be paid more attention by neurologists.

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