Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series

BMC Neurol. 2021 Jan 11;21(1):12. doi: 10.1186/s12883-020-02040-4.


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.

Keywords: Hereditary spastic paraplegia; Mild cognitive impairment; Next generation sequencing; SPG11.

MeSH terms

  • Adolescent
  • Adult
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / genetics
  • DNA Mutational Analysis / methods
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Mutation
  • Proteins / genetics
  • Spastic Paraplegia, Hereditary / complications*
  • Spastic Paraplegia, Hereditary / diagnosis*
  • Young Adult


  • Proteins
  • SPG11 protein, human

Supplementary concepts

  • Spastic paraplegia 11, autosomal recessive