Hereditary Spastic Paraplegias

Keywords Disease name and synonyms Definition Classification Differential diagnosis Prevalence Clinical description Management including treatment Diagnostic methods Etiology Genetic counseling Antenatal diagnosis References Abstract Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. Clinically, HSPs can be divided into two main groups: pure and complex forms. Pure HSPs are characterized by slowly progressive lower extremity spasticity and weakness, often associated with hypertonic urinary disturbances, mild reduction of lower extremity vibration sense, and, occasionally, of joint position sensation. Complex HSP forms are characterized by the presence of additional neurological or non-neurological features. Pure HSP is estimated to affect 9.6 individuals in 100.000. HSP may be inherited as an autosomal dominant, autosomal recessive or X-linked recessive trait, and multiple recessive and dominant forms exist. The majority of reported families (70-80%) displays autosomal dominant inheritance, while the remaining cases follow a recessive mode of transmission. To date, 24 different loci responsible for pure and complex HSP have been mapped. Despite the large and increasing number of HSP loci mapped, only 9 autosomal and 2 X-linked genes have been so far identified, and a clear genetic basis for most forms of HSP remains to be elucidated.