Dominant Centronuclear Myopathy with Early Childhood Onset due to a Novel Mutation in BIN1

Autosomal dominant centronuclear myopathy (CNM) caused by mutations in the gene coding for amphiphysin-2 (BIN1) typically presents in adulthood with progressive muscle weakness. We report a Dutch family with AD CNM due to a novel BIN1 mutation (c.53T>A (p.Val18Glu)), strongly impairing the membrane tubulation activity of amphiphysin-2. The main features were mild proximal weakness with pronounced myalgia, exercise intolerance and large muscle mass, with a childhood onset in the youngest generation and mild cognitive features. This suggests BIN1 mutations should be considered in patients with isolated exercise intolerance and myalgia, even in childhood.