ABSTRACT
BACKGROUND: Hereditary spastic paraparesis (HPS) linked to mutations in the spastin gene (SPG4) is considered to be a pure form of spastic hereditary paraparesis. However, in this disease also other signs of central nervous system involvement are frequently found. METHODS: Clinical, genetical and neuroradiological investigations were carried out in a large family with autosomal dominant spastic paraparesis and in a sporadic case with spastic paraparesis. RESULTS: Additional clinical and molecular data are provided, studying other members of the same pedigree, as already described, with a five-base deletion in exon 9 of the SPG4 gene (1215-1219delTATAA) whose members show MRI anomalies that fall within the Dandy-Walker continuum. Furthermore, an unrelated female patient with hypoplasia of the cerebellar vermis is indicated, carrying a de novo previously reported mutation of the SPG4 gene (c.1741C>T p.R581X). CONCLUSIONS: Spastin may play an important role in the development of the central nervous system and in particular in the development of the structures of posterior fossa.