{"doi":"10.1002/mds.29225","title":"<scp>Early‐Onset</scp> and Severe Complex Hereditary Spastic Paraplegia Caused by <i>De Novo</i> Variants in <scp><i>SPAST</i></scp>","abstract":"BACKGROUND: Familial hereditary spastic paraplegia (HSP)-SPAST (SPG4) typically presents with a pure HSP phenotype. OBJECTIVE: The aim of this study was to delineate the genotypic and phenotypic spectrum of children with de novo HSP-SPAST. METHODS: This study used a systematic cross-sectional analysis of clinical and molecular features. RESULTS: We report the clinical and molecular spectrum of 40 patients with heterozygous pathogenic de novo variants in SPAST (age range: 2.2-27.7 years). We identified 19 unique variants (16/40 carried the same recurrent variant, p.Arg499His). Symptom onset was in early childhood (median: 11.0 months, interquartile range: 6.0 months) with significant motor and speech delay, followed by progressive ascending spasticity, dystonia, neurogenic bladder dysfunction, gastrointestinal dysmotility, and epilepsy. The mean Spastic Paraplegia Rating Scale score was 32.8 ± 9.7 (standard deviation). CONCLUSIONS: These results confirm that de novo variants in SPAST lead to a severe and complex form of HSP that differs from classic familial pure HSP-SPAST. Clinicians should be aware of this syndrome in the differential diagnosis for cerebral palsy. © 2022 International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2022,"id":254714,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7819,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":879690,"name":"Afshin Saffari","orcid":"0000-0003-4119-7519","position":1,"is_corresponding":false},{"id":880278,"name":"Melanie Kellner","orcid":null,"position":2,"is_corresponding":false},{"id":327685,"name":"Marion Döbler‐Neumann","orcid":null,"position":3,"is_corresponding":false},{"id":767001,"name":"Catherine Jordan","orcid":"0000-0003-0099-1142","position":4,"is_corresponding":false},{"id":371860,"name":"Siddharth Srivastava","orcid":"0000-0001-7008-1879","position":5,"is_corresponding":false},{"id":447518,"name":"Bo Zhang","orcid":"0000-0003-1574-198X","position":6,"is_corresponding":false},{"id":40872,"name":"Mustafa Sahin","orcid":"0000-0001-7044-2953","position":7,"is_corresponding":false},{"id":901878,"name":"John K. Fink","orcid":"0000-0002-8039-530X","position":8,"is_corresponding":false},{"id":901879,"name":"Linsley Smith","orcid":"0000-0002-3672-900X","position":9,"is_corresponding":false},{"id":281492,"name":"Jennifer E. Posey","orcid":"0000-0003-4814-6765","position":10,"is_corresponding":false},{"id":368828,"name":"Katharine E. Alter","orcid":"0000-0002-5405-2143","position":11,"is_corresponding":false},{"id":901880,"name":"Camilo Toro","orcid":"0000-0001-7139-0518","position":12,"is_corresponding":false},{"id":326725,"name":"Craig Blackstone","orcid":"0000-0003-1261-9655","position":13,"is_corresponding":false},{"id":360802,"name":"Ariane Soldatos","orcid":"0000-0003-3570-5230","position":14,"is_corresponding":false},{"id":902427,"name":"Michelle Christie","orcid":null,"position":15,"is_corresponding":false},{"id":350235,"name":"Rebecca Schüle","orcid":"0000-0002-7781-2766","position":16,"is_corresponding":false},{"id":584752,"name":"Darius Ebrahimi‐Fakhari","orcid":"0000-0002-0026-4714","position":17,"is_corresponding":false},{"id":879691,"name":"Alisa Mo","orcid":"0000-0002-6435-1227","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:25:08.518416Z","pmid":"36103453","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}