Novel TPM3 mutation in a family with cap myopathy and review of the literature.
Cap myopathy is a rare congenital myopathy characterized by the presence of caps within muscle fibres and caused by mutations in ACTA1, TPM2 or TPM3. Thus far, only three cases with TPM3-related cap myopathy have been described. Here, we report on the first autosomal dominant family with cap myopathy in three-generations, caused by a novel heterozygous mutation in the alpha-tropomyosin-slow-encoding gene (TPM3; exon 4; c.445C>A; p.Leu149Ile). The three patients experienced first symptoms of muscle weakness in childhood and followed a slowly progressive course. They presented generalized hypotrophy and mild muscle weakness, elongated face, high arched palate, micrognathia, scoliosis and respiratory involvement. Intrafamilial variability of skeletal deformities, respiratory involvement and mild cardiac abnormalities was noted. Muscle MRI revealed a recognizable pattern of fatty muscle infiltration and masseter muscle hypertrophy. Subsarcolemmal caps were present in 6-10% of the fibres and immunoreactive with anti-tropomyosin antibodies. We conclude that the MRI-pattern of muscle involvement and the presence of masseter muscle hypertrophy in cap myopathy may guide molecular genetic diagnosis towards a mutation in TPM3. Regular respiratory examinations are important, even if patients have no anamnestic clues. We compare our findings to all cases of cap myopathy with identified mutations (n=11), thus far reported in the literature.
Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany; Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany.
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Schreckenbach
Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany.
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JM
Schröder
Institut de Myologie, Université Pierre et Marie Curie Paris, UM76, INSERM U 974, CNRS UMR 7215, Paris, France.
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T
Voit
Medizinisch Genetisches Zentrum München, München, Germany.
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A
Abicht
Institute of Neuropathology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
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Neuen-Jacob
Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany; JARA Translational Brain Medicine, Germany.
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A
Roos
Medizinisch Genetisches Zentrum München, München, Germany.
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S
Bulst
Department of Radiology, University Hospital RWTH Aachen, Aachen, Germany.
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C
Kuhl
Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany; JARA Translational Brain Medicine, Germany.
J B
JB
Schulz
Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany; JARA Translational Brain Medicine, Germany.
J
J
Weis
Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany; Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany; JARA Translational Brain Medicine, Germany. Electronic address: kclaeys@ukaachen.de.
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Claeys
D000328:Adult; D000368:Aged; D003937:Diagnosis, Differential; D018450:Disease Progression; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D006984:Hypertrophy / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008406:Masseter Muscle / Q000002:abnormalities / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D014335:Tropomyosin / Q000235:genetics*; D055815:Young Adult
C498783:TPM3 protein, human; D014335:Tropomyosin
Alpha tropomyosin slow; Caps; Congenital myopathy; Genotype–phenotype correlations; Muscle fibre inclusions; Whole-body muscle MRI