Hereditary Spastic Paraplegy Associated with the AP4S1 Gene: A Case Series Highlighting Diagnostic Pitfalls and Phenotypic Variability.

ABSTRACT:

Introduction

Complex hereditary spastic paraplegias (HSPs) are defined by progressive spasticity with diverse neurological manifestations, complicating the diagnostic process. Pathogenic variants in genes encoding subunits of the adaptor protein complex-4 (AP4), including the AP4S1 gene, have been implicated in a subset of HSPs.

Case presentation

We report three siblings with complex HSP harboring pathogenic AP4S1 gene variants, focusing on the clinical characteristics and the diagnostic challenges and pitfalls. The patients exhibited common clinical features such as progressive spasticity, distinctive craniofacial features, and neurodevelopmental delays. Neuroimaging findings included agenesis of the corpus callosum and ventricular enlargement in two siblings,

SUBMITTER: Gunay C 

PROVIDER: S-EPMC12500296 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature