Clinical signs and symptoms in a large hereditary spastic paraparesis pedigree with a novel spastin mutation

Autor: Elizabeth O'Hearn, Dung Tsa Chen, Anthony P. Nicholas, Russell L. Margolis, Susan E. Holmes
Rok vydání: 2004
Předmět:
Zdroj: Movement Disorders. 19:641-648
ISSN: 1531-8257
0885-3185
DOI: 10.1002/mds.20077
Popis: The most common form of autosomal dominant hereditary spastic paraparesis (HSP), SPG4, is caused by mu- tations in the spastin gene on chromosome 2p. This disease is characterized by intra- and interfamilial phenotypic variation. To determine the predictive values of clinical signs and symp- toms in SPG4, we examined 43 members of a large pedigree with autosomal dominant HSP. We then identified the genetic etiology of the disorder in this family, a novel nonsense muta- tion in exon 1 of spastin, carried by 24 of the examined family members. The best clinical predictors of positive gene status were the presence of hyperreflexia in the lower extremities, 2 beats of ankle clonus, pes cavus, bladder symptoms and in- creased tone in the legs. The mean age of onset was 32.2 7.4 years, but the age of onset was earlier in children from 10 of 12 child-parent gene-positive pairs, with a mean difference of 10.8 3.3 years. The finding of leg weakness was especially common in older-onset affected family member with leg hy- perreflexia. These results suggest that specific clinical signs and symptoms may be of value in differentiating individuals af- fected with SPG4 from family members with nonspecific neu- rological findings. © 2004 Movement Disorder Society
Databáze: OpenAIRE
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