Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults

Robert W. Loar, J. Martijn Bos, Melissa L. Will, Steve R. Ommen, Michael John Ackerman

Research output: Contribution to journalArticle

7 Citations (Scopus)

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. Methods and 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 ± 7.4mm, 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.

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalCongenital Heart Disease
Volume10
Issue number6
DOIs
StatePublished - Nov 1 2015

Fingerprint

Hypertrophic Cardiomyopathy
Genetic Association Studies
Young Adult
Genotype
Genetic Testing
Tertiary Care Centers
Phenotype
Electronic Health Records
Sudden Cardiac Death
Cardiovascular Diseases
Heart Failure
Transplantation
Morbidity
Transplants

Keywords

  • Genotype
  • Hypertrophic Cardiomyopathy
  • Phenotype
  • Young

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pediatrics, Perinatology, and Child Health
  • Surgery
  • Radiology Nuclear Medicine and imaging

Cite this

Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults. / Loar, Robert W.; Bos, J. Martijn; Will, Melissa L.; Ommen, Steve R.; Ackerman, Michael John.

In: Congenital Heart Disease, Vol. 10, No. 6, 01.11.2015, p. 529-536.

Research output: Contribution to journalArticle

Loar, Robert W. ; Bos, J. Martijn ; Will, Melissa L. ; Ommen, Steve R. ; Ackerman, Michael John. / Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults. In: Congenital Heart Disease. 2015 ; Vol. 10, No. 6. pp. 529-536.
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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. Methods and 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 ± 7.4mm, 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.",
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AU - Ommen, Steve R.

AU - Ackerman, Michael John

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N2 - 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. Methods and 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 ± 7.4mm, 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.

AB - 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. Methods and 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 ± 7.4mm, 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.

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KW - Hypertrophic Cardiomyopathy

KW - Phenotype

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