Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias

• Published in: Scientific reports Vol. 11; no. 1; p. 22248
• Main Authors: Giordani, Gabriela Marchisio, Diniz, Fabrício, Fussiger, Helena, Gonzalez-Salazar, Carelis, Donis, Karina Carvalho, Freua, Fernando, Ortega, Roberta Paiva Magalhães, de Freitas, Julian Letícia, Barsottini, Orlando Graziani Povoas, Rosemberg, Sergio, Kok, Fernando, Pedroso, José Luiz, França, Marcondes Cavalcante, Saute, Jonas Alex Morales
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-11-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/208/1516; 631/208/514; 631/378; 631/378/1689; 631/378/2583; 692/617; 692/617/375; Adolescent; Adult; Age; Age of Onset; Alleles; Ataxia; Brazil - epidemiology; Child; Children; Clinical trials; Cohort Studies; Collaboration; Differential diagnosis; Disease; Disease Management; Disease Susceptibility; Epidemiology; Female; Genetic Predisposition to Disease; Genetic screening; Genomics; Genotype; Hereditary spastic paraplegia; High-Throughput Nucleotide Sequencing; Hospitals; Humanities and Social Sciences; Humans; Magnetic Resonance Imaging; Male; Medical records; multidisciplinary; Mutation; Paralysis; Phenotype; Population Surveillance; Rare diseases; Science; Science (multidisciplinary); Spastic Paraplegia, Hereditary - diagnosis; Spastic Paraplegia, Hereditary - epidemiology; Spastic Paraplegia, Hereditary - etiology; Spasticity; Spastin - genetics; Survival analysis; Symptom Assessment; Wheelchairs; Young Adult; Brazil
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-01635-2

The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%)
.
Missense pathogenic variants in
SPAST
were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional
Spastic Paraplegia Rating Scale
progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases.