Severe dilated cardiomyopathy and quadriceps myopathy due to lamin A/C gene mutation: a phenotypic study.
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.
Charniot
Jean-Christophe
JC
Service de Cardiologie, Avicenne Hospital, Paris XIII University, Bobigny, France. jean-christophe.charniot@avc.ap-hop-paris.fr
Desnos
Michel
M
Zerhouni
Khaled
K
Bonnefont-Rousselot
Dominique
D
Albertini
Jean-Paul
JP
Salama
Jeffrey Zaketto
JZ
Bassez
Guillaume
G
Komajda
Michel
M
Artigou
Jean-Yves
JY
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D052097:Quadriceps Muscle
C494847:LMNA protein, human; D034904:Lamin Type A