Severe dilated cardiomyopathy and quadriceps myopathy due to lamin A/C gene mutation: a phenotypic study

Eur J Heart Fail. 2006 May;8(3):249-56. doi: 10.1016/j.ejheart.2005.08.007. Epub 2005 Nov 28.

Abstract

This study reports a family affected by a new phenotype associated with dilated cardiomyopathy and quadriceps myopathy.

Methods: 29 family members underwent a physical and neurological examination, including an electromyogram and biopsy of muscle abnormalities. A cardiac examination was performed in all subjects.

Results: The family pedigree (n=72) demonstrated that transmission was autosomal dominant. Eleven subjects had cardiac involvement, only four had quadriceps muscle involvement. Cardiac impairment preceded neurological involvement. The mean age for neurological involvement was 44+/-0.8 years (range 43-45) and cardiac involvement was 37+/-7.9 years (range: 24-45). Cardiac involvement consisted of: hypokinetic dilated cardiomyopathy (64%); atrial fibrillation (100%); ventricular arrhythmias (64%); impaired conduction with bundle branch or complete atrio ventricular block (73%). Four patients required pacemakers and anti arrhythmic therapies. Four patients died: two of refractory heart failure and two of sudden death; two patients were resuscitated following cardiac arrest. Three patients required a prophylactic implantable cardiac defibrillator (ICD). Muscle morphological abnormalities were characterized by a variable number of fibers with rimmed vacuoles. The quadriceps deteriorated progressively without impairment of other muscles. Genotypic study showed a lamin A/C gene mutation.

Conclusions: This family was affected by a new phenotype composed of an autosomal dominant severe dilated cardiomyopathy with conduction defects or arrhythmias and quadriceps myopathy. Cardiac abnormalities preceded neuromuscular disorders and defined the prognosis of this disease.

MeSH terms

  • Adult
  • Cardiomyopathy, Dilated / genetics*
  • Female
  • Humans
  • Lamin Type A / genetics*
  • Male
  • Middle Aged
  • Muscular Diseases / genetics*
  • Mutation*
  • Phenotype
  • Quadriceps Muscle*

Substances

  • LMNA protein, human
  • Lamin Type A