Brain Advance Access originally published online on June 9, 2005
Brain 2005 128(10):2315-2326; doi:10.1093/brain/awh576
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Myotilinopathy: refining the clinical and myopathological phenotype
1 Institut de Neuropatologia, IDIBELL-Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain, 2 The National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1361, USA and 3 Muskellabor, Department of Neurology, University of Bonn, 53105 Bonn, Germany
Correspondence to: Dr Montse Olivé, Institut de Neuropatologia, IDIBELL-Hospital de Bellvitge, C/Feixa Llarga s/n, 08907 Hospitalet de Llobregat, Barcelona, Spain E-mail: 25169mop{at}comb.es
Mutations in myotilin gene (MYOT) have been associated with variable syndromes including limb girdle muscular dystrophy type 1A (LGMD1A) and a subgroup of myofibrillar myopathy (MFM/MYOT). We studied six Spanish patients from three unrelated kindreds and seven patients without family history. Three previously reported and two novel disease-associated MYOT mutations were identified in this group of patients. The disease is characterized by the onset at the age of 42–77 years with muscle weakness initially in distal or proximal leg muscles, eventually spreading to other muscle groups of the lower and upper extremities. Associated signs of cardiomyopathy, respiratory failure and peripheral neuropathy are present in a fraction of patients. Myopathological features of focal myofibrillar destruction resulting in intracytoplasmic deposits, strongly immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemmally located non-rimmed vacuoles and streaming Z-lines, were observed in each patient studied. The Spanish cohort, the largest group of patients studied so far, shares phenotypic features with both LGMD1A and MFM/MYOT variants thus establishing a continuum of phenotypic manifestations characteristic of myotilinopathy, an emerging neuromuscular disorder.
Key Words: LGMD1A; myofibrillar myopathy; myotilin; MYOT mutations; phenotype
Abbreviations: CK = creatinine kinase; EKG = electrocardiography; EMG = electromyography; IBM = inclusion body myositis; LGMD1A = limb girdle muscular dystrophy type 1A; MFM = myofibrillar myopathy; MYOT = myotilin gene; MRC = Medical Research Council; MHC = major histocompatibilty complex; RBBB = right bundle branch block; ZASP = Z-band alternatively spliced PDZ motif-containing protein
Received February 9, 2005. Revised April 27, 2005. Accepted May 20, 2005.
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