title: Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies caused by dystrophin defects.
abstract: OBJECTIVE
  We sought to describe the diagnostic work-up, phenotype, and long-term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS) defects.
  
  
  BACKGROUND
  X-linked DCM associated with DYS defects can be clinically indistinguishable from other types of DCM.
  
  
  METHODS
  The series comprises 436 consecutive male patients diagnosed with DCM. Patients underwent endomyocardial biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and multiple ligation dependent probe assay for deletions and direct sequencing of the 79 exons and flanking regions of the gene for point mutations or small rearrangements.
  
  
  RESULTS
  We identified DYS defects in 34 of 436 patients (7.8%) (onset age 34 ± 11 years, age range 17 to 54 years); 30 had proven X-linked inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site mutation. During a median follow-up of 60 months (interquartile range: 11.25 to 101.34 months) we observed 17 events, all related to heart failure (HF) (median event-free survival: 83.5 months). Eight patients (23%) underwent transplantation, and 9 (26%) died of HF while waiting for transplantation. Eight patients received an implantable cardioverter-defibrillator, although none had device intervention during a median follow-up of 14 months (interquartile range: 5 to 25 months). No patient died suddenly, suffered syncope, or developed life-threatening ventricular arrhythmias.
  
  
  CONCLUSIONS
  DYS-related DCM should be suspected in male patients with increased serum creatine phosphokinase (82%) and X-linked inheritance. The disease shows a high risk of end-stage HF but a lower risk of life-threatening arrhythmias.
authors.affiliation: Centre for Inherited Cardiovascular Diseases, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Policlinico San Matteo, Pavia, Italy; Department of Pediatric Sciences and Human Pathology, University of Pavia, Pavia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Diegoli
authors.forename: Maurizia
authors.initials: M
authors.lastname: Grasso
authors.forename: Valentina
authors.initials: V
authors.lastname: Favalli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Serio
authors.forename: Fabiana Isabella
authors.initials: FI
authors.lastname: Gambarin
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Michele
authors.initials: M
authors.lastname: Pasotti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Agozzino
authors.forename: Laura
authors.initials: L
authors.lastname: Scelsi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
authors.forename: Oreste
authors.initials: O
authors.lastname: Febo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piccolo
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
mesh_terms: D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics*; D005500:Follow-Up Studies; D050172:Genes, X-Linked / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: D016189:Dystrophin