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

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.