• N Deconinck, P Richard, V Allamand, A Behin, P Lafôret, A Ferreiro, A de Becdelievre, C Ledeuil, C Gartioux, I Nelson, R Y Carlier, P Carlier, K Wahbi, N Romero, M T Zabot, F Bouhour, V Tiffreau, A Lacour, B Eymard, and T Stojkovic.
• Department of Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Bruxelles, Belgium AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Centre de référence des maladies neuromusculaires, Paris Est, France.
• J. Neurol. Neurosurg. Psychiatr. 2015 Dec 1;86(12):1337-46.

ObjectiveMutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype correlations and long-term follow-up description in BM remain scarce.MethodsWe retrospectively evaluated the long-term clinical evolution, and genotype-phenotype correlations in 35 genetically identified BM patients (23 index cases).ResultsNineteen patients showed a typical clinical picture with contractures, proximal weakness and slow disease progression while 11 presented a more severe evolution. Five patients showed an atypical presentation, namely a limb girdle muscle weakness in 2 and a congenital myopathy pattern with either no contractures, or only limited to ankles, in 3 of them. Pathogenic COL6A1-3 mutations were mostly missense or in frame exon-skipping resulting in substitutions or deletions. Twenty one different mutations were identified including 12 novel ones. The mode of inheritance was, autosomal dominant in 83% of the index patients (including 17% (N=4) with a de novo mutation), recessive in 13%, and undetermined in one patient. Skipping of exon 14 of COL6A1 was found in 35% of index cases and was mostly associated with a severe clinical evolution. Missense mutations were detected in 39% of index cases and associated with milder forms of the disease.ConclusionsLong-term follow-up identified important phenotypic variability in this cohort of 35 BM patients. However, worsening of the functional disability appeared typically after the age of 40 in 47% of our patients, and was frequently associated with COL6A1 exon 14 skipping.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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