Diseases title

Hereditary spastic paraplegia )

Test molecule
Orpha Number: 685
Familial spastic paraplegia, Hereditary spastic paraparesis, HSP, SPG, Strümpell-Lorrain disease

Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. HSP is estimated to affect 1 in 20 000 individuals in the general population of Europe, with variable frequencies in distinct populations (from 1.3 to 9/100 000 individuals). 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. 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%) display autosomal dominant inheritance, while the remaining cases follow a recessive mode of transmission. To date, 31 different loci responsible for pure and complex HSP have been mapped. Despite the large and increasing number of HSP loci mapped, only eleven autosomal and two X-linked genes have been identified so far, and a clear genetic basis for most forms of HSP remains to be elucidated. Diagnosis is based on clinical examination. However, additional explorations (imaging, electroencephalogram, long-chain fatty acid measurements, electromyogram, and serology for human T-cell lymphotropic virus type 1 (HTLVI)) are required to exclude the differential diagnoses for this syndrome (multiple sclerosis, vitamin B12 deficiency, dopa-responsive dystonia, amyotrophic or primary lateral sclerosis, ascending hereditary spastic paralysis and spastic paraplegia caused by HTLVI infection). Management is symptomatic (myorelaxing medication, functional rehabilitation).
source: Orphanet