Medical genetics serves as a bridge between basic medical science and clinical courses. With its complex curriculum and abstract concepts, traditional lecture-based teaching often leads to difficulties in comprehension, diminishes students’ interest in learning, and results in poor teaching outcomes. Incorporating typical case studies into instruction can make genetic theories more tangible, enhance students’ intuitive understanding, facilitate their grasp of abstract concepts, and boost their interest in learning. Hereditary spastic paraplegia (HSP) is a group of hereditary neurological disorders characterized by progressive spastic paraplegia of both lower limbs. As a monogenic disorder, hereditary spastic paraplegia exhibits high genetic heterogeneity. To date, more than 80 distinct disease-causing genes have been identified, encompassing various inheritance patterns such as autosomal dominant, autosomal recessive, and X-linked recessive inheritance; Hereditary spastic paraplegia has been included in China’s first batch of rare disease listings, creating a need for genetic counseling. Prenatal diagnosis and differential diagnosis typically require integration with genetic testing. Case-based teaching focused on hereditary spastic paraplegia can comprehensively cover the core concepts of medical genetics and help students develop a complete clinical genetic reasoning process from clinical phenotype to family analysis, genetic diagnosis, and risk assessment. Based on this educational philosophy, members in our teaching team explored teaching materials focusing on the genetic characteristics of HSP, including disease genes, genetic effect of mutation, pathogenesis, inheritance patterns, genetic diagnosis, and clinical treatment to construct a comprehensive, integrated case-based teaching framework and incorporated it throughout the teaching practice of medical genetics. Teachers implemented this instructional design in their medical genetics courses, transforming abstract theoretical instruction into accessible case-based teaching, which stimulated students’ interest in learning and enhanced their ability to understand theories related to genetic diseases. This teaching reform facilitated the effective integration of genetic knowledge with clinical applications, fostered the development of clinical reasoning and research literacy among medical students, and provided an innovative method for medical genetics teaching.