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.
Paediatric-onset hereditary spastic paraplegias: a retrospective cohort study / Schiavoni, S.; Spagnoli, C.; Rizzi, S.; Salerno, G. G.; Frattini, D.; Pisani, F.; Fusco, C.. - In: DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. - ISSN 0012-1622. - (2020). [10.1111/dmcn.14547]
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