Hereditary Spastic Paraplegia Overview
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower extremities due to pyramidal tract dysfunction (1). HSP can be associated with brisk reflexes, extensor plantar reflexes, and urinary urgency (2). Clinically, HSP can be classified as “complicated” or “complex” if the patient presents with other neurological and systemic features in addition to HSP, such as ataxia, dystonia, intellectual disability, dementia, optic atrophy, retinitis pigmentosa, epilepsy, muscular atrophy, deafness, ichthyosis, and short stature. HSP can be classified as pure or uncomplicated if no additional findings are present (2). Age of onset of HSP can range from early childhood to late adulthood. In early onset cases spasticity is typically more prominent than muscle weakness, and motor delays may be observed (3). For later onset cases, muscle weakness may be more marked, and symptoms may progress more rapidly compared to early onset cases (3). HSP has been estimated to have a prevalence of 1-10 individuals per 100,000 (4).
Hereditary Spastic Paraplegia Etiology
HSP is a highly genetically heterogeneous group of disorders (4). 70-80% of HSP is inherited in an autosomal dominant manner, and the majority of dominant HSP is classified as uncomplicated or pure HSP (2). Autosomal recessive, X-linked and mitochondrial inheritance can also be observed in HSP.
Clinical Utility of Genetic Testing for Hereditary Spastic Paraplegia
Genetic testing for HSP can present challenges, due to the wide clinical and genetic heterogeneity that exists. Determining the molecular basis of disease using genetic testing can be useful in predicting prognosis and disease course, and can aid in identification of at-risk family members. Utilizing whole exome sequencing technology for the Hereditary Spastic Paraplegia Exome Panel test allows us to have a dynamic gene list that can be updated regularly as new genes are identified.