Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients

Eur J Hum Genet. 2013 Nov;21(11):1312-5. doi: 10.1038/ejhg.2013.27. Epub 2013 Feb 27.

Abstract

Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the 'ears-of the lynx'-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 3-4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology
  • Disease Progression*
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Mutation / genetics
  • Netherlands
  • Phenotype
  • Proteins / genetics
  • Spastic Paraplegia, Hereditary / genetics
  • Spastic Paraplegia, Hereditary / pathology*
  • Young Adult

Substances

  • Proteins
  • SPG11 protein, human

Supplementary concepts

  • Spastic paraplegia 11, autosomal recessive