In:
Movement Disorders, Wiley, Vol. 37, No. 12 ( 2022-12), p. 2440-2446
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0885-3185
,
1531-8257
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2041249-6
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