title: Spongious hypertrophic cardiomyopathy in patients with mutations in the four-and-a-half LIM domain 1 gene.
abstract: BACKGROUND
  X-linked myopathy with postural muscle atrophy is a novel X-linked myopathy caused by mutations in the four-and-a-half LIM domain 1 gene (FHL1). Cardiac involvement was suspected in initial publications. We now systematically analyzed the association of the FHL1 genotype with the cardiac phenotype to establish a potential cardiac involvement in the disease.
  
  
  RESULTS
  Seventeen male patients and 23 female mutation carriers were compared with healthy controls. Every patient underwent a comprehensive clinical and cardiovascular workup. ECG abnormalities occurred frequently in affected males and were less frequent in heterozygous females. Both male and female mutation carriers had increased myocardial mass (affected males=115.1±25.3 g/m(2); heterozygous females=95.1±19.6 g/m(2); controls=89.0±15.6 g/m(2) and 72.6±12.6 g/m(2); respectively) with increased wall thickness (typically midventricular and apical segments) mainly in affected males. Longitudinal systolic function was reduced in affected males (radial systolic strain: affected males=24.6±11.8%; male controls=43.2±14.8%; P=0.002). Diastolic dysfunction occurred in both affected males and heterozygous females. Cardiac MRI revealed a morphological hallmark of X-linked myopathy with postural muscle atrophy; a characteristic spongious structure and replacement fibrosis indicated by late enhancement could be detected in most affected males. X-linked myopathy with postural muscle atrophy was associated with reduced exercise capacity in affected males but not in heterozygous female mutation carriers.
  
  
  CONCLUSIONS
  X-linked myopathy with postural muscle atrophy patients consistently showed electrical, functional, and characteristic morphological cardiac abnormalities that translate into reduced exercise capacity. Reduced systolic and diastolic function is associated with a novel type of spongious hypertrophic cardiomyopathy. An unexpected finding was that some cardiac abnormalities were also present in heterozygous female mutation carriers.
authors.affiliation: Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
authors.forename: Josepha S
authors.initials: JS
authors.lastname: Binder
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.forename: Markus
authors.initials: M
authors.lastname: Niemann
authors.forename: Wolfram
authors.initials: W
authors.lastname: Machann
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
authors.forename: Gernot
authors.initials: G
authors.lastname: Plank
authors.forename: Albrecht
authors.initials: A
authors.lastname: Schmidt
authors.forename: Egbert
authors.initials: E
authors.lastname: Bisping
authors.forename: Ivana
authors.initials: I
authors.lastname: Poparic
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lafer
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.forename: Stefan
authors.initials: S
authors.lastname: Quasthoff
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
authors.forename: Rainer
authors.initials: R
authors.lastname: Rienmueller
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
authors.forename: Andrea
authors.initials: A
authors.lastname: Berghold
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.forename: Christian
authors.initials: C
authors.lastname: Windpassinger
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001794:Blood Pressure / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D050172:Genes, X-Linked; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D060588:LIM Domain Proteins / Q000737:chemistry / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000503:physiopathology; D009154:Mutation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D016276:Ventricular Function; D000083143:X-Linked Emery-Dreifuss Muscular Dystrophy
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms