title: Genotype-Phenotype Correlations in Apical Variant Hypertrophic Cardiomyopathy.
abstract: OBJECTIVE
  Hypertrophic cardiomyopathy is underscored by profound phenotypic and genotypic heterogeneity. Echocardiographically, hypertrophic cardiomyopathy can be categorized into four morphological subtypes: reverse curve, sigmoidal, neutral contour, and apical variant. Previous studies indicate that reverse curve hypertrophic cardiomyopathy is the strongest predictor of a positive genetic test. Little is known about the spectrum and prevalence of mutations and genotype-phenotype correlations in apical hypertrophic cardiomyopathy.
  
  
  METHODS
  Between 1999 and 2007, 1053 patients with the diagnosis of hypertrophic cardiomyopathy (60% male, age at diagnosis 44.4 ± 19 years) underwent sarcomeric genetic testing. Blinded to the genetic test results, each echocardiogram was scored for septal morphology and phenotyping was performed using the patient's medical record. Subset analysis was performed to elucidate the genotype, phenotype, and outcome of apical hypertrophic cardiomyopathy.
  
  
  RESULTS
  Overall, 71 patients (7%) had apical hypertrophic cardiomyopathy on echocardiography (63% male, mean age 47.8 ± 15 years, mean left ventricular wall thickness 19.8 ± 6 mm). Left ventricular outflow tract obstruction was uncommon (seven patients; 10%). Eighteen patients (25%) had a positive genetic test, with the majority of mutations found in MYBPC3 (six; 35%) and MYH7 (six; 35%). Follow-up was available on 68 patients (96%) with a median age of 57.3 years (range 19.3-82 years). Mean follow-up was 5.5 years (range 0.1-18.2 years). There was no statistical difference between the occurrence rates of adverse events between genotype-positive and genotype-negative groups.
  
  
  CONCLUSIONS
  In this largest cohort of patients with genetic testing for hypertrophic cardiomyopathy, <10% exhibited apical disease. This least common subtype was associated with a negative genetic test result 75% of the time. In contrast to prior publications suggesting a predilection for ACTC1/TPM1 mutations in patients with apical hypertrophic cardiomyopathy, the two most common genotypes (MYBPC3-HCM and MYH7-HCM) remained most common among patients who had a positive genetic test.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Towe
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minn, USA.
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Bos
authors.affiliation: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Steve R
authors.initials: SR
authors.lastname: Ommen
authors.affiliation: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minn, USA.|Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minn, USA.|Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000145:classification / Q000235:genetics* / Q000628:therapy; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016896:Treatment Outcome
keywords: Adult; Apical Hypertrophic Cardiomyopathy; Congenital Heart Disease; Genetic Testing; Hypertrophic Cardiomyopathy