Premium
Paediatric‐onset hereditary spastic paraplegias: a retrospective cohort study
Author(s) -
Schiavoni Silvia,
Spagnoli Carlotta,
Rizzi Susanna,
Salerno Grazia G,
Frattini Daniele,
Pisani Francesco,
Fusco Carlo
Publication year - 2020
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.14547
Subject(s) - hereditary spastic paraplegia , exome sequencing , genetic heterogeneity , medicine , genetics , spastic , cohort , pediatrics , genetic testing , genotype , phenotype , bioinformatics , biology , gene , pathology , cerebral palsy , physical therapy
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.