What question did this study set out to answer?

This research aims to expand the understanding of HACE1 loss-of-function variants associated with spastic paraplegia and improve clinical management.

February 14, 2026Open Access

Expanding the repertoire of loss-of-function variants in HACE1 causing complex spastic paraplegia: literature review and recommendations on clinical management

Key Points

This research aims to expand the understanding of HACE1 loss-of-function variants associated with spastic paraplegia and improve clinical management.
Reviewed literature to collect and analyze cases of HACE1 related spastic paraplegia.
Added eight new clinical cases from five unrelated families.
Integrated clinical and phenotypic data to assess overlaps and variability among cases.
Total of 40 cases documented, from 22 families, with HACE1 related spastic paraplegia.
Defined a phenotypic spectrum and highlighted gaps in clinical feature reporting.
Provided recommendations for standardized clinical management and documentation.

Abstract

This study adds eight new cases of HACE1 related spastic paraplegia from five unrelated families to the literature, bringing the total to 40 cases from 22 families. By integrating clinical data from our cohort with the published reports, we defined the phenotypic spectrum linked to HACE1 disruption, noting key overlaps and variability, and highlighted gaps in reporting clinical features. It also provides clinical management recommendations and calls for standardized phenotypic documentation to strengthen genotype-phenotype correlations.

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Cite This Study

Yousaf et al. (Wed,) studied this question.

synapsesocial.com/papers/699010942ccff479cfe56e6a https://doi.org/https://doi.org/10.1186/s40246-026-00914-1

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