Miriam L Giarrana1, Pascal Joset2, Heinrich Sticht3, Stephanie Robb4, Katharina Steindl2, Anita Rauch2, Andrea Klein1. 1. Department of Paediatric Neurology, University Children's Hospital, Steinwiesstrasse 75, 8032, Zürich, Switzerland. 2. Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Zurich, Switzerland. 3. Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. 4. Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children, London, UK.
Abstract
INTRODUCTION: Congenital myasthenic syndromes are rare. Mutations in MUSK were first described in 2004. Thirteen patients have been reported to date, mostly with a relatively mild course. The molecular diagnosis has implications for choice of treatment and genetic counseling. METHODS: Clinical course and electrophysiological, pathological, and genetic findings were assessed. RESULTS: We describe the case of a boy with prenatal onset and severe respiratory symptoms with a persisting need for ventilation. The patient had severe bulbar symptoms, marked axial weakness causing a "dropped head," and some facial and proximal weakness. Ophthalmoparesis developed during the first year of life. Salbutamol led to improvement, 3,4-diaminopyridine had a modest effect, but pyridostigmine produced deterioration. Two novel mutations in MUSK were found by whole exome sequencing. CONCLUSIONS: We expand the phenotype of congenital myasthenic syndromes with MUSK mutations, describing a more severe clinical course with prenatal onset. Predominant bulbar and respiratory weakness with facial and axial weakness and ophthalmoparesis are diagnostic clues.
INTRODUCTION:Congenital myasthenic syndromes are rare. Mutations in MUSK were first described in 2004. Thirteen patients have been reported to date, mostly with a relatively mild course. The molecular diagnosis has implications for choice of treatment and genetic counseling. METHODS: Clinical course and electrophysiological, pathological, and genetic findings were assessed. RESULTS: We describe the case of a boy with prenatal onset and severe respiratory symptoms with a persisting need for ventilation. The patient had severe bulbar symptoms, marked axial weakness causing a "dropped head," and some facial and proximal weakness. Ophthalmoparesis developed during the first year of life. Salbutamol led to improvement, 3,4-diaminopyridine had a modest effect, but pyridostigmine produced deterioration. Two novel mutations in MUSK were found by whole exome sequencing. CONCLUSIONS: We expand the phenotype of congenital myasthenic syndromes with MUSK mutations, describing a more severe clinical course with prenatal onset. Predominant bulbar and respiratory weakness with facial and axial weakness and ophthalmoparesis are diagnostic clues.
Authors: Pedro M Rodríguez Cruz; Judith Cossins; Jonathan Cheung; Susan Maxwell; Sandeep Jayawant; Ruth Herbst; Dominic Waithe; Alexandr P Kornev; Jacqueline Palace; David Beeson Journal: Hum Mutat Date: 2019-11-25 Impact factor: 4.878