Rapid disease progression found
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 course of the disease in 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.
SOURCE: Eur J Hum Genet. 2013 Feb 27. doi: 10.1038/ejhg.2013.27. [Epub ahead of print] PMID: 23443022 [PubMed – as supplied by publisher]
Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients.
de Bot ST, Burggraaff RC, Herkert JC, Schelhaas HJ, Post B, Diekstra A, van Vliet RO, van der Knaap MS, Kamsteeg EJ, Scheffer H, van de Warrenburg BP, Verschuuren-Bemelmans CC, Kremer HP.
Department of Neurology, Radboud University, Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.