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Eur J Hum Genet ; 21(11): 1312-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23443022

RESUMO

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.


Assuntos
Progressão da Doença , Paraplegia Espástica Hereditária/patologia , Adolescente , Adulto , Encéfalo/patologia , Seguimentos , Fundo de Olho , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mutação/genética , Países Baixos , Fenótipo , Proteínas/genética , Paraplegia Espástica Hereditária/genética , Adulto Jovem
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