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

Article type: Case Report

Authors: Kouwenberg, Carlyn^{a; 1} | Bohm, Johann^{b; 1} | Erasmus, Corrie^c | van Balken, Irene^a | Vos, Sandra^d | Kusters, Benno^e | Kamsteeg, Erik-Jan^f | Biancalana, Valerie^{b; g} | Koch, Catherine^b | Dondaine, Nicolas^g | Laporte, Jocelyn^{b; 2} | Voermans, Nicol^{a; 2; *}

Affiliations: [a] Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud university medical centre, Nijmegen, The Netherlands | [b] Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg Illkirch, Strasbourg, France | [c] Department of Pediatric Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands | [d] Department of Medical Psychology, Radboud University Medical Centre, Nijmegen, The Netherlands | [e] Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands | [f] Department of Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands | [g] Laboratoire Diagnostic Génétique, Faculté de Médecine – CHRU, Strasbourg, France

Correspondence: [*] Correspondence to: N.C. Voermans, MD, PhD, Neurologist, Radboud University Medical Centre, Neurology, 935, P.O. Box 9101, 6500 HB Nijmegen. The Netherlands. Tel.: +0031 243616600; Fax: +0031 243541122; E-mail: [email protected].

Note: [1] Shared first authorship

Note: [2] Shared last authorship

Abstract: 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.

Keywords: Dominant centronuclear myopathy, BIN1 mutation, childhood onset

DOI: 10.3233/JND-170238

Journal: Journal of Neuromuscular Diseases, vol. 4, no. 4, pp. 349-355, 2017