Die hereditären spastischen Spinalparalysen

Zusammenfassung

Die hereditären spastischen Spinalparalysen (HSP) sind eine genetisch definierte Krankheitsgruppe mit dem Hauptmerkmal der langsam progredienten Paraspastik. Nach dem klinischen Symptommuster werden „reine” und „komplizierte” Formen unterschieden. Die „reine” HSP zeigt klinisch nur eine Pyramidenbahnschädigung, die „komplizierten” Formen weisen - zusätzlich zur Paraspastik als Kernsymptomatik - akzessorische Symptome auf. Die Differenzialdiagnostik der HSP umfasst entzündliche, degenerative und metabolische Erkrankungen sowie strukturelle Veränderungen im Bereich des Schädels oder Spinalkanals. Die HSP sind genetisch komplex. Autosomal-dominante (70 - 80 % aller Familien), autosomal-rezessive und x-chromosomal rezessive Erbgänge sind bekannt. Für die autosomal-dominante Verlaufsform sind bisher Genorte auf Chromosom 2, 8, 10, 12, 14, 15 und 19 gefunden worden. Ein Gen auf Chromosom 2 konnte geklont und als Genprodukt das Protein Spastin definiert werden. Bei der autosomal-rezessiven HSP ist bislang ein Kandidatengen bekannt, das Paraplegin auf Chromosom 16. Daneben existieren weitere Genorte auf Chromosom 3, 8 und 15. Bei der seltenen x-chromosomal vererbten HSP wurden Mutationen im L1-CAM-Gen und im Proteolipid-Protein-Gen beschrieben. Die Rolle aller bisher bekannten Gene in der Pathogenese der Erkrankung ist noch unklar. Es ist zu erwarten, dass es in Zukunft zu einer Neueinteilung des Krankheitsbildes auf der Basis des jeweiligen Gen- und Stoffwechseldefektes kommen wird.

The Hereditary Spastic Paraplegias - Classification and Molecular Genetics

The hereditary spastic paraplegias are a genetically defined group of disorders characterized by slowly progressive spastic paraparesis. Depending on the clinical presentation they are classified as „pure” or „complicated”. The „pure” form shows spastic paraplegia in isolation, while the complicated form is characterized by additional major clinical features. The differential diagnosis includes inflammatory, degenerative and metabolic disorders as well as structural abnormalities of brain and spinal cord. The HSP are genetically complex. Autosomal dominant (70 - 80 % of all families), autosomal recessive and X-linked inheritance patterns have been described. For autosomal dominant HSP, genetic loci on chromosome 2, 8, 10, 12, 14, 15 and 19 have been found. A gene on chromosome 2 has been cloned, the gene product is a protein called spastin. For autosomal recessive HSP, the protein paraplegin could be identified as a candidate gene on chromosome 16. In addition to this, there are genetic loci on chromosome 3, 8 and 15. In X-linked HSP, mutations in the L1 CAM gene and the proteolipid proteine gene have been described. The pathogenetic role of the genes known so far is not clear. In the near future, a new classification of HSP based on genetic and metabolic defects can be expected.

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