Motor and respiratory heterogeneity in Duchenne patients: Implication for clinical trials

被引：106

作者：

Humbertclaude, Veronique ^{[1
,2
]}

Hamroun, Dalil ^{[1
,2
]}

Bezzou, Kamel ^{[3
]}

Berard, Carole ^{[4
]}

Boespflug-Tanguy, Odile ^{[5
]}

Bommelaer, Christine ^{[5
]}

Campana-Salort, Emmanuelle ^{[6
]}

Cances, Claude ^{[7
]}

Chabrol, Brigitte ^{[8
]}

Commare, Marie-Christine ^{[9
]}

Cuisset, Jean-Marie ^{[10
]}

de Lattre, Capucine ^{[4
,11
]}

Desnuelle, Claude ^{[12
]}

Echenne, Bernard ^{[13
]}

Halbert, Cecile ^{[8
]}

Jonquet, Olivier ^{[14
]}

Labarre-Vila, Annick ^{[15
]}

N'Guyen-Morel, Marie-Ange ^{[16
]}

Pages, Michel ^{[17
]}

Pepin, Jean-Louis ^{[18
]}

Petitjean, Thierry ^{[11
]}

Pouget, Jean ^{[6
]}

Ollagnon-Roman, Elisabeth ^{[19
]}

Richelme, Christian ^{[20
]}

Rivier, Francois ^{[13
]}

Sacconi, Sabrina ^{[12
]}

Tiffreau, Vincent ^{[21
]}

Vuillerot, Carole ^{[4
]}

Picot, Marie-Christine ^{[3
]}

Claustres, Mireille ^{[1
,2
,22
]}

Beroud, Christophe ^{[1
,2
,22
]}

Tuffery-Giraud, Sylvie ^{[2
,22
]}

机构：

[1] CHU Montpellier, Genet Mol Lab, F-34000 Montpellier, France

[2] INSERM, U827, F-34000 Montpellier, France

[3] CHU Montpellier, Unite Rech Clin, F-34000 Montpellier, France

[4] Hosp Civils Lyon, Serv Reeduc Pediat, F-69677 Bron, France

[5] CHU Hotel Dieu, Serv Genet Clin, F-63058 Clermont Ferrand, France

[6] CHU La Timone, Serv Neurol & Malad Neuromusculaires, F-13385 Marseille, France

[7] Hop Enfants, Serv Neurol Pediat, F-31059 Toulouse, France

[8] CHU La Timone, Serv Neurol Pediat, F-13385 Marseille, France

[9] CHU Couple Enfant, Serv Reeduc Pediat, F-38043 Grenoble, France

[10] CHU Salengro, Serv Neurol Pediat, Ctr Reference Malad Neuromusculaires, F-59037 Lille, France

[11] CHU Croix Rousse, Ctr Reference Malad Neuromusculaires Adultes, Serv Reanimat Med & Assistance Resp, F-69004 Lyon, France

[12] CHU Archet 1, Ctr Reference Malad Neuromusculaires, F-06202 Nice, France

[13] CHU Gui de Chauliac, Ctr Reference Malad Neuromusculaires Grand Sud Ou, Serv Neurol Pediat, F-34000 Montpellier, France

[14] CHU Gui de Chauliac, Serv Reanimat Med, F-34295 Montpellier, France

[15] CHU La Tronche, Ctr Reference Malad Neuromusculaires, Serv Neurol, F-38043 Grenoble, France

[16] CHU La Tronche, Clin Univ Pediat, F-38043 Grenoble, France

[17] CHU Gui de Chauliac, Serv Neurol, F-34295 Montpellier, France

[18] CHU Michallon, Serv Explorat Fonct Cardioresp, F-38043 Grenoble, France

[19] CHU Croix Rousse, F-69004 Lyon, France

[20] CHU Lenual, Serv Pediat, F-06200 Nice, France

[21] CHU Swynghedauw, Ctr Reference Malad Neuromusculaires, Serv Med Phys & Readaptat, F-59037 Lille, France

[22] Univ Montpellier I, UFR Med, F-34000 Montpellier, France

来源：

EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY | 2012年 / 16卷 / 02期

关键词：

Duchenne muscular dystrophy; Phenotype; Database; Locus-specific database; DMD gene; MUSCULAR-DYSTROPHY; CUMULATIVE INCIDENCE; COMPETING RISKS; PHENOTYPE; CHILDREN; PARAMETERS; SCOLIOSIS; DATABASE; STAGE; TIME;

D O I：

10.1016/j.ejpn.2011.07.001

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Aims: Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD). Methods: The French dystrophinopathy database provided clinical, histochemical and molecular data of 278 DMD patients (mean longitudinal follow-up: 14.2 years). Diagnosis was based on mutation identification in the DMD gene. Three groups were defined according to the age at ambulation loss: before 8 years (group A); between 8 and 11 years (group B); between 11 and 16 years (group C). Results: Motor and respiratory declines were statistically different between the three groups, as opposed to heart involvement. When acquired, running ability was lost at the mean age of 5.41 (group A), 7.11 (group B), 9.19 (group C) years; climbing stairs ability at 6.24 (group A), 7.99 (group B), 10,42 (group C) years, and ambulation at 7.10 (group A), 9.25 (group B), 12.01 (group C) years. Pulmonary growth stopped at 10.26 (group A), 12.45 (group B), 14.58 (group C) years. Then, forced vital capacity decreased at the rate of 8.83 (group A), 7.52 (group B), 6.03 (group C) percent per year. Phenotypic variability did not rely on specific mutational spectrum. Conclusion: Beside the most common form of DMD (group B), we provide detailed description on two extreme clinical subgroups: a severe one (group A) characterized by early severe motor and respiratory decline and a milder subgroup (group C). Compared to group B or C, four to six times fewer patients from group A are needed to detect the same decrease in disease progression in a clinical trial. (C) 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

引用

页码：149 / 160

页数：12

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