Posterior fossa abnormalities in hereditary spastic paraparesis with spastin mutations

J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):440-3. doi: 10.1136/jnnp.2008.154807.

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.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Codon / genetics
  • Cognition / physiology
  • Cranial Fossa, Posterior / abnormalities*
  • Cranial Fossa, Posterior / pathology*
  • Dandy-Walker Syndrome / genetics
  • Dandy-Walker Syndrome / pathology
  • Electroencephalography
  • Electromyography
  • Exons / genetics
  • Female
  • Humans
  • Infant
  • Intellectual Disability / etiology
  • Intellectual Disability / genetics
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Neuropsychological Tests
  • Pedigree
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology*
  • Spastic Paraplegia, Hereditary / psychology
  • Spastin
  • Young Adult

Substances

  • Codon
  • Adenosine Triphosphatases
  • Spastin
  • SPAST protein, human