Résumé :
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Innovative therapies are presently being developed for DMD. Evaluating their effect will require precise knowledge of both the natural history and factors influencing the course of a disease which can be no longer considered as homogeneous in terms of severity and neurological prognosis. We investigated 75 steroid-free patients without muscle dystrophin at immunohistochemistry and immunoblotting, first detected at the St Vincent de Paul hospital and followed by the same medical team every 6 months for a mean follow-up >10yrs. We used multivariate analyses, hierarchical clustering, and logistic regression, with 3 aims: (i) detecting correlations between motor, cognitive, cardiac and respiratory variables; (ii) delineating homogenous subgroups with similar evolution; and (iii) identifying early clinical predictive factors for classification in each subgroup. Cognitive and motor variables provided a factor model with a best 4-cluster solution: group A (congenital DMD, 20%) very poor intellectual and motor outcomes; group B (classical DMD, 28%) intermediate intellectual and poor motor outcomes; group C (late onset DMD, 22%) normal intelligence and delayed motor impairment; and D (pure motor DMD, 30%) normal intelligence and poor motor outcome. Group A patients also had more severe respiratory and cardiac involvement. Mutations before exon 30 increased in proportion from group A to D, but, except for the well established link between mental retardation and the involvement of the N terminal part of the gene, particularly the DP71 transcript, no clinical-genetic correlation could be identified between motor function and type and location of mutations, suggesting some influence of, as yet unknown, epigenetic factors on motor severity. Early predictive outcome indicators were “age at initial symptoms <2yrs” combined with “psychomotor delay as initial symptom” for congenital DMD, and lower limb manual muscle testing (MMT) score >6 at 8yrs for late onset DMD. Then, IQ categorically segregated pure motor from classical DMD patients.
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