title: Limb girdle muscular dystrophy due to LAMA2 mutations: diagnostic difficulties due to associated peripheral neuropathy.
abstract: We report an eleven year old girl with early motor difficulties initially diagnosed with a peripheral neuropathy in another hospital based on abnormal electrophysiological findings. Our clinical assessment did not highlight obvious clinical features supporting a peripheral neuropathy but evidence of mild proximal weakness. Electrophysiological studies performed at our hospital revealed evidence of a sensorimotor demyelinating polyneuropathy with possible axonal involvement. Brain magnetic resonance imaging (MRI) revealed subtle white matter signal abnormalities, interpreted as nonspecific. Given the patient's proximal weakness and a mildly elevated serum creatine kinase, we performed a muscle biopsy. The muscle had mildly dystrophic features and subtly depleted laminin α2 expression. There was diffusely upregulated laminin α5 expression, and depletion of laminin α2 in intramuscular motor nerves, which made us suspect a partial laminin α2 (merosin) deficiency. Muscle MRI showed predominant posterior and medial compartments involvement. The patient was found to have autosomal recessively inherited double heterozygous LAMA2 mutations. This case illustrates the mild end of the partial merosin deficiency phenotypic spectrum, and highlights how careful assessment of laminin α2 expression in intramuscular motor nerves can be a helpful diagnostic clue in partial merosin deficiency.
authors: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, United Kingdom.
authors: Sophelia H S
authors: SH
authors: Chan
authors: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, United Kingdom.
authors: A Reghan
authors: AR
authors: Foley
authors: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, United Kingdom.
authors: Rahul
authors: R
authors: Phadke
authors: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, United Kingdom.
authors: Ann Agnes
authors: AA
authors: Mathew
authors: Department of Clinical Neurophysiology, Great Ormond Street Hospital, London WC1N 3JH, United Kingdom.
authors: Matthew
authors: M
authors: Pitt
authors: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, United Kingdom; RJAH Orthopaedic Hospital, Oswestry SY10 7AG, United Kingdom.
authors: Caroline
authors: C
authors: Sewry
authors: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, United Kingdom. Electronic address: f.muntoni@ucl.ac.uk.
authors: Francesco
authors: F
authors: Muntoni
mesh_terms: D001706:Biopsy; D001921:Brain / Q000473:pathology; D018389:Codon, Nonsense; D003937:Diagnosis, Differential; D005260:Female; D006579:Heterozygote; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D018389:Codon, Nonsense; D007797:Laminin; C102645:laminin alpha 2
keywords: Congenital muscular dystrophy; Laminin α2; Laminin α5; Limb girdle muscular dystrophy; Merosin-deficient; Peripheral neuropathy