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

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 tonicclonic with upper limbs myoclonic seizures and eyelid myoclonia with absences). Second, opposed to previous descriptions, seizures might not always be drug responsive. (c) 2021 Elsevier Ltd. All rights reserved.

Automated summary

SPG6 is considered a pure autosomal dominant hereditary spastic paraplegia (AD-HSP), but complex cases have also been reported with comorbidities such as epilepsy. A common pathogenic variant in SPG6 is found to be associated with drug-resistant eyelid myoclonia with absences, suggesting a diverse clinical spectrum. Seizures in SPG6 may not always respond to medication, contrary to previous descriptions.