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

Unlabelled: 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.