Paediatric-onset hereditary spastic paraplegias: a retrospective cohort study

Silvia Schiavoni, Carlotta Spagnoli, Susanna Rizzi, Grazia G Salerno, Daniele Frattini, Francesco Pisani, Carlo Fusco

Research output: Contribution to journalArticlepeer-review

Abstract

AIM: To describe the clinical and neurogenetic spectrum of paediatric-onset hereditary spastic paraplegias (HSPs) diagnosed in our unit.

METHOD: We report on 47 patients (30 males, 17 females; mean [SD] age 12y 7mo [6y 2mo], range 4-34y) clinically diagnosed with an HSP at the Child Neurology Unit, IRCCS-ASMN (Reggio Emilia, Italy) between 1990 and 2018, who were genetically investigated by means of single-gene direct sequencing and/or next-generation sequencing technologies (targeted panels, whole-exome sequencing [WES]).

RESULTS: Complex forms prevailed slightly (n=26), autosomal dominant being the main inheritance pattern (n=11), followed by recessive (n=5) and X-linked (n=1). A definite genetic diagnosis was achieved in 17 patients. Spastic paraplegia 3A (n=4) was the most frequent cause of autosomal dominant HSP in our cohort, while no genetic variant prevailed in autosomal recessive forms and pathogenic/likely pathogenic variants were disclosed in a wide range of different genes.

INTERPRETATION: We found wide phenotypic and genetic heterogeneity. With increasing accessibility to WES, a higher number of patients receive a diagnosis, allowing detection of variants in ultra-rare disease-causing genes and refining genotype-phenotype correlations.

WHAT THIS PAPER ADDS: A genetic diagnosis of paediatric-onset hereditary spastic paraplegia was achieved in one-third of patients. Pathogenic/likely pathogenic variants in rare genes were found. Genotypic and phenotypic heterogeneity favours targeted panel/whole-exome sequencing for diagnosis.

Original languageEnglish
Pages (from-to)1068-1074
Number of pages7
JournalDevelopmental Medicine and Child Neurology
Volume62
Issue number9
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Phenotype
  • Retrospective Studies
  • Spastic Paraplegia, Hereditary/diagnosis
  • Young Adult

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