Bethlem Myopathy Phenotypes and Follow Up: Description of 8 Patients at the Mildest End of the Spectrum

Article type: Research Article

Authors: Cruz, Simao^{a; b} | Figueroa-Bonaparte, Sebastian^{a; c} | Gallardo, Eduard^{a; c} | de Becdelièvre, Alix^d | Gartioux, Corine^e | Allamand, Valérie^e | Piñol, Patricia^{a; c} | Garcia, Maria Angels Rodriguez^f | Jiménez-Mallebriera, Cecilia^f | Llauger, Jaume^g | González-Rodríguez, Lidia^{c; h} | Cortes-Vicente, Elena^{a; c} | Illa, Isabel^{a; c} | Díaz-Manera, Jordi^{a; c; *}

Affiliations: [a] Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau de Barcelona, Universitat Autónoma de Barcelona, Spain | [b] Department of Neurology, Hospital Prof, Doutor Fernando Fonseca, Amadora, Portugal | [c] Centro de Investigación Básica en Red en Enfermedaded Raras (CIBERER), Spain | [d] Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France | [e] Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS974, CNRS FRE3617, Center for Research in Myology, Institut de Myologie, GH Pitié-Salpêtrière, Paris, France | [f] Neuromuscular Disorders Unit, Neurology Department, Hospital Sant Joan de Déu, Barcelona, Spain | [g] Department of Radiology, Hospital de la Santa Creu I Sant Pau de Barcelona, Universitat Autónoma de Barcelona, Spain | [h] Department of Genetic, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain

Correspondence: [*] Correspondence to: Dr. Jordi Díaz Manera, Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, C/Sant Antoni M” Claret 167, PC: 08025, Barcelona, Spain. Tel.: +34 935565986; E-mail: [email protected].

Abstract: The classical phenotypes of collagen VI-associated myopathies are well described. Little is known, however, about the progression of patients at the mildest end of the clinical spectrum. In this report, we describe the clinical findings and the results of MRI, muscle biopsy, collagen VI expression in cultured skin fibroblasts and genetic tests of a series of patients with Bethlem myopathy. Our series highlights the existence of mild presentations of this disorder that progresses only slightly and can easily be overlooked. Analysis of the genetic studies suggests that missense mutations can be associated to a milder clinical presentation. Muscle MRI is extremely useful as it shows a pathognomonic pattern in most patients, especially those with some degree of muscle weakness.

Keywords: Bethlem disease, collagen VI deficiency, muscle dystrophy, muscle MRI, Ulrich disease

DOI: 10.3233/JND-150135

Journal: Journal of Neuromuscular Diseases, vol. 3, no. 2, pp. 267-274, 2016