Clinical phenotype, muscle MRI and muscle pathology of LGMD1F
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Of the seven autosomal dominant genetically distinct forms of LGMD so far described, in only four the causative gene has been identified (LGMD1A-1D). We describe clinical, histopathological and muscle MRI features of a large Italo-Spanish kindred with LGMD1F presenting proximal-limb and axial muscle weakness. We obtained complete clinical data and graded the progression of the disease in 29 patients. Muscle MRI was performed in seven patients. Three muscle biopsies from two patients were investigated. Patients with age at onset in the early teens, had a more severe phenotype with a rapid disease course; adult onset patients presented a slow course. Muscle MRI showed prominent atrophy of lower limb muscles, involving especially the vastus lateralis. Widening the patients population resulted in the identification of previously unreported features, including dysphagia, arachnodactyly and respiratory insufficiency. Muscle biopsies showed diffuse fibre atrophy, which evolved with time, chronic myopathic changes, basophilic cytoplasmic areas, autophagosomes and accumulation of myofibrillar and cytoskeletal proteins. The LGMD1F is characterized by a selective involvement of limb muscles with respiratory impairment in advanced stages, and by different degrees of clinical progression. Novel clinical features emerged from the investigation of additional patients.
KeywordsLimb girdle muscular dystrophy LGMD1F Clinical phenotype Muscle MRI
The authors wish to thank all the family members who promoted meetings for neuromuscular examination and blood sample collection. This work was supported by grants from the Association Française contre les Myopathies (13859 to MF, 14999 and 16216 to CA) and the Telethon Italy (GTB12001 and GUP10006 to CA and GUP11006 to UN).
Conflicts of interest
The authors declare that they have no conflict of interest.
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