title: Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disease and a leading cause of identifiable sudden cardiac death (SCD) in the young. Herein, we sought to determine the genotype-phenotype correlations in a cohort of unrelated, genotyped patients diagnosed with HCM at a young age, as well as to characterize the differences between HCM diagnosed in adulthood and HCM diagnosed at a young age.
  
  
  RESULTS
  From 1999 to 2011, 1053 unrelated patients diagnosed with HCM were enrolled in research-based genetic testing. The electronic medical record was reviewed to identify those with HCM diagnosed at ≤21 years (N = 137, mean age at diagnosis 13.2 ± 6 years, 64% male). From this cohort of patients recruited from a tertiary care referral center, the genetic test was positive in 71 (52%), which was significantly higher than patients diagnosed >21 years (31%; P < .001). Genotype-positive patients had increased maximum left ventricular wall thickness (24.9 ± 8.0 vs. 21.6 ± 7.4 mm, P = .01) and higher incidence of reverse-curve ventricular septal morphology (71% vs. 40%, P < .001). Unrelated to genotype status, 26/137 patients (19%) experienced significant HCM-related morbidity/mortality including progressive heart failure symptoms in 12, transplantation in 4, and death in 10.
  
  
  CONCLUSIONS
  Among patients diagnosed with HCM during the first two decades of life, the yield of genetic testing is significantly higher than when diagnosed at later age. While the phenotype of young HCM patients is worse than patients whose HCM is diagnosed at later age, the phenotypes of genotype-positive and genotype-negative young patients were similar. Independent of genotype, nearly 30% of the patients with follow-up in this study had symptom progression, transplant, or death.
authors.affiliation: Children's Medical Center, Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Loar
authors.affiliation: Department of Molecular Pharmacology & 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: J Martijn
authors.initials: JM
authors.lastname: Bos
authors.affiliation: Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Will
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: Children's Medical Center, Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minn, USA.|Department of Molecular Pharmacology & 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: D000293:Adolescent; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D004247:DNA / Q000032:analysis; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004247:DNA
keywords: Genotype; Hypertrophic Cardiomyopathy; Phenotype; Young