Dominant BIN1-related centronuclear myopathy (CNM) revealed by lower limb myalgia and moderate CK elevation

We report a BIN1-related CNM family with unusual clinical phenotype. The proband, a 56-year-old man suffered of lower limbs myalgia since the age of 52. Clinical examination showed short stature, mild symmetric eyelid ptosis without ophthalmoplegia, scapular winging and Achilles tendon retraction. A muscle weakness was not noted. CK levels were up to 350 UI/L. Deltoid muscle biopsy showed nuclear centralization and clustering, deep sarcolemmal invaginations and type 1 fiber hypotrophy. Whole body MRI revealed fatty infiltration of posterior legs compartments, lumbar paraspinal and serratus muscles. Myotonic dystrophy type1 and 2, Pompe disease and MTM1 and DNM2-related CNM were ruled out. By sequencing BIN1, we identified a heterozygous pathogenic mutation [c.107C > A (p.A36E)], and we demonstrate that the mutation strongly impairs the membrane tubulation property of the protein. One affected sister carried the same mutation. Her clinical examination and muscle MRI revealed a similar phenotype. Our findings expand the clinical and genetic spectrum of the autosomal dominant CNM associated with BIN1 mutations.