SPG6 (NIPA1 variant): A report of a case with early-onset complex hereditary spastic paraplegia and brief literature review

J Clin Neurosci. 2021 Dec;94:281-285. doi: 10.1016/j.jocn.2021.10.026. Epub 2021 Nov 9.

Abstract

SPG6, caused by NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome) gene pathogenic variants, is mainly considered as a pure autosomal dominant hereditary spastic paraplegia (AD-HSP), even if descriptions of complex cases have also been reported. We detected the common c.316G > A, p.(Gly106Arg) pathogenic de novo substitution in a 10-year-old patient with HSP and drug-resistant eyelid myoclonia with absences. In order to assess the significance of this association, we reviewed the literature to find that 25/110 (23%) SPG6 cases are complex, including a heterogeneous spectrum of comorbidities, in which epilepsy is most represented (10%), but also featuring peripheral neuropathy (5.5%), amyotrophic lateral sclerosis (3.6%), memory deficits (3.6%) or cognitive impairment (2.7%), tremor (2.7%) and dystonia (0.9%). From this literature review and our single case experience, two main conclusions can be drawn. First, SPG6 is an AD-HSP with both pure and complex presentation, and frequent occurrence of epilepsy within the spectrum of genetic generalized epilepsies (absences, bilateral tonic-clonic, bilateral tonic-clonic with upper limbs myoclonic seizures and eyelid myoclonia with absences). Second, opposed to previous descriptions, seizures might not always be drug responsive.

Keywords: Autosomal dominant; Complex; Epilepsy; Hereditary spastic paraplegia; NIPA1; Pure; SPG6.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • Epilepsy*
  • Humans
  • Membrane Proteins / genetics
  • Mutation, Missense
  • Spastic Paraplegia, Hereditary* / diagnosis
  • Spastic Paraplegia, Hereditary* / genetics

Substances

  • Membrane Proteins
  • NIPA1 protein, human

Supplementary concepts

  • Spastic paraplegia 6, autosomal dominant