Limb girdle muscular dystrophy due to LAMA2 mutations: Diagnostic difficulties due to associated peripheral neuropathy

• Published in: Neuromuscular disorders : NMD Vol. 24; no. 8; pp. 677 - 683
• Main Authors: Chan, Sophelia H.S., Foley, A. Reghan, Phadke, Rahul, Mathew, Ann Agnes, Pitt, Matthew, Sewry, Caroline, Muntoni, Francesco
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.08.2014
• Subjects: Biopsy; Brain - pathology; Codon, Nonsense; Congenital muscular dystrophy; Diagnosis, Differential; Female; Heterozygote; Humans; Laminin - genetics; Laminin α2; Laminin α5; Limb girdle muscular dystrophy; Magnetic Resonance Imaging; Merosin-deficient; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Dystrophies, Limb-Girdle - diagnosis; Muscular Dystrophies, Limb-Girdle - genetics; Muscular Dystrophies, Limb-Girdle - pathology; Muscular Dystrophies, Limb-Girdle - physiopathology; Neural Conduction; Neurology; Peripheral Nervous System Diseases - diagnosis; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - pathology; Peripheral Nervous System Diseases - physiopathology; Peripheral neuropathy; Limb girdle muscular dystrophy; Laminin α5; Peripheral neuropathy; Congenital muscular dystrophy; Laminin α2; Merosin-deficient
• ISSN: 0960-8966; 1873-2364; 1873-2364
• DOI: 10.1016/j.nmd.2014.05.008

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.