Childhood-Onset Hereditary Spastic Paraplegia (HSP): A Case Series and Review of Literature

Pediatr Neurol. 2022 May:130:7-13. doi: 10.1016/j.pediatrneurol.2022.02.007. Epub 2022 Mar 3.


Background: Hereditary spastic paraplegia (HSP) encompasses several rare genetic disorders characterized by progressive lower extremity spasticity and weakness caused by corticospinal tract degeneration. Published literature on genetically confirmed pediatric HSP cases is limited.

Methods: We conducted a retrospective review of childhood-onset HSP cases followed in the neuromuscular clinics at Children's and Emory Healthcare in Atlanta. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, genetic test results, comorbidities, and treatment were recorded.

Results: Sixteen patients with HSP (eight males, eight females) with a mean age 19 years ± 15.7 years were included. Ten patients (66%) presented with gait difficulty. Seven (44%) were ambulatory at the last clinic follow-up visit with an average disease duration of 7.4 years. Genetically confirmed etiologies included SPAST (3 patients), MARS (2), KIF1A (2), KIF5A (1), SACS (1), SPG7 (1), REEP1 (1), PNPT1 (1), MT-ATP6 (1), and ATL1 (1). Symptom onset to genetic confirmation on an average was 8.2 years. Sensory motor axonal polyneuropathy was found in seven patients, and two exhibited cerebellar atrophy on magnetic resonance imaging (MRI) of the brain. Neurological comorbidities included developmental delay (n = 9), autism (n = 5), epilepsy (n = 3), and attention-deficit/hyperactivity disorder (n = 2).

Conclusions: In our study, a significant proportion (70%) of subjects with childhood-onset HSP had comorbid neurocognitive deficits, polyneuropathy with or without neuroimaging abnormalities, and rare genetic etiology. Genetic diagnosis was established either through inherited genetic neuropathy panel or whole-exome sequencing, which supports the utility of whole-exome sequencing in aiding in HSP diagnosis.

Keywords: Attention-deficit/hyperactivity disorder; Autism spectrum disorder; Developmental delay; Epilepsy; Hereditary spastic paraplegia; Peripheral neuropathy.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Exome Sequencing
  • Exoribonucleases / genetics
  • Female
  • Humans
  • Kinesins
  • Male
  • Membrane Transport Proteins / genetics
  • Mutation
  • Neuroimaging
  • Spastic Paraplegia, Hereditary* / diagnosis
  • Spastic Paraplegia, Hereditary* / genetics
  • Spastin / genetics
  • Young Adult


  • KIF1A protein, human
  • KIF5A protein, human
  • Membrane Transport Proteins
  • REEP1 protein, human
  • Exoribonucleases
  • PNPT1 protein, human
  • Spastin
  • Kinesins
  • SPAST protein, human