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.
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 DMDpatients (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.
Authors: Luca Bello; Kevin M Flanigan; Robert B Weiss; Pietro Spitali; Annemieke Aartsma-Rus; Francesco Muntoni; Irina Zaharieva; Alessandra Ferlini; Eugenio Mercuri; Sylvie Tuffery-Giraud; Mireille Claustres; Volker Straub; Hanns Lochmüller; Andrea Barp; Sara Vianello; Elena Pegoraro; Jaya Punetha; Heather Gordish-Dressman; Mamta Giri; Craig M McDonald; Eric P Hoffman Journal: Am J Hum Genet Date: 2016-10-13 Impact factor: 11.025
Authors: Rebecca J Willcocks; William T Triplett; Donovan J Lott; Sean C Forbes; Abhinandan Batra; H Lee Sweeney; Jerry R Mendell; Krista Vandenborne; Glenn A Walter Journal: Muscle Nerve Date: 2018-01-24 Impact factor: 3.217
Authors: Emma Ciafaloni; Anil Kumar; Ke Liu; Shree Pandya; Christina Westfield; Deborah J Fox; Kristin M Caspers Conway; Christopher Cunniff; Katherine Mathews; Nancy West; Paul A Romitti; Michael P McDermott Journal: J Pediatr Rehabil Med Date: 2016
Authors: Jennifer G Andrews; Molly M Lamb; Kristin Conway; Natalie Street; Christina Westfield; Emma Ciafaloni; Dennis Matthews; Christopher Cunniff; Shree Pandya; Deborah J Fox Journal: J Neuromuscul Dis Date: 2018
Authors: Janneke C van den Bergen; Monika Hiller; Stefan Böhringer; Linda Vijfhuizen; Hendrika B Ginjaar; Amina Chaouch; Kate Bushby; Volker Straub; Mariacristina Scoto; Sebahattin Cirak; Véronique Humbertclaude; Mireille Claustres; Chiara Scotton; Chiara Passarelli; Hanns Lochmüller; Francesco Muntoni; Sylvie Tuffery-Giraud; Alessandra Ferlini; Annemieke M Aartsma-Rus; Jan J G M Verschuuren; Peter Ac 't Hoen; Pietro Spitali Journal: J Neurol Neurosurg Psychiatry Date: 2014-12-04 Impact factor: 10.154
Authors: David J Birnkrant; Katharine Bushby; Carla M Bann; Benjamin A Alman; Susan D Apkon; Angela Blackwell; Laura E Case; Linda Cripe; Stasia Hadjiyannakis; Aaron K Olson; Daniel W Sheehan; Julie Bolen; David R Weber; Leanne M Ward Journal: Lancet Neurol Date: 2018-02-03 Impact factor: 44.182