A Rare Homozygous AP4S1 Variant in Rwandan Siblings with Autosomal Recessive Hereditary Spastic Paraplegia Type 52 (SPG52).

Background/

Objectives

Hereditary spastic paraplegia type 52 (SPG52) is a rare, inherited neurodevelopmental condition passed down in an autosomal recessive pattern. In this report, we describe two siblings from Rwanda who exhibited classic signs of the disorder, including progressive lower-limb spasticity, significant delays in motor development, and exaggerated deep tendon reflexes.

Methods

Genetic testing through Whole-Exome Sequencing (WES) reveals a rare homozygous splice-site variant (NM_001128126.3:c.295-3C>A) in the AP4S1 gene.

Results

Despite the severity of symptoms, both children responded positively to treatment with muscle relaxants and regular physiotherapy. Notably, MRI scans of the brain and spine showed no structural abnormalities.

Conclusions

By documenting this case, we add to the growing understanding of SPG52, particularly within under-represented Sub-Saharan African populations, and underscore the critical role of early genetic testing in guiding timely diagnosis and intervention.