Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST.
Mov Disord
; 37(12): 2440-2446, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36103453
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraplegia Espástica Hereditária
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
Idioma:
En
Revista:
Mov Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos