title: Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1.
abstract: Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non-dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL-1 disorder in X-linked cardiomyopathy.
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: I
authors: I
authors: San Román
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: M
authors: M
authors: Navarro
authors: Neurology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: F
authors: F
authors: Martínez
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: L
authors: L
authors: Albert
authors: Pathology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: L
authors: L
authors: Polo
authors: Pneumology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: J
authors: J
authors: Guardiola
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: E
authors: E
authors: García-Molina
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: C
authors: C
authors: Muñoz-Esparza
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: J M
authors: JM
authors: López-Ayala
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.|Internal Medicine Department, University of Murcia, Murcia, Spain.
authors: M
authors: M
authors: Sabater-Molina
authors: Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.|Internal Medicine Department, University of Murcia, Murcia, Spain.
authors: J R
authors: JR
authors: Gimeno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D016027:Heart Transplantation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060588:LIM Domain Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D012737:Sex Factors; D013921:Thrombocytopenia / Q000503:physiopathology; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D003402:Creatine Kinase
keywords: Emery-Dreifuss muscular dystrophy; FHL1; cardiomyopathy; mutation