Erin M Miller1, Robert B Hinton2, Richard Czosek2, Angela Lorts2, Ashley Parrott2, Amy R Shikany2, Richard F Ittenbach2, Stephanie M Ware2. 1. From the Division of Cardiology (E.M.M., R.B.H., R.C., A.L., A.P., A.R.S.) and Division of Biostatistics and Epidemiology (R.F.I.), Cincinnati Children's Hospital Medical Center, OH; and Department of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis (S.M.W.). erin.miller@cchmc.org. 2. From the Division of Cardiology (E.M.M., R.B.H., R.C., A.L., A.P., A.R.S.) and Division of Biostatistics and Epidemiology (R.F.I.), Cincinnati Children's Hospital Medical Center, OH; and Department of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis (S.M.W.).
Abstract
BACKGROUND: Left ventricular noncompaction (LVNC) can occur in isolation or can co-occur with a cardiomyopathy phenotype or cardiovascular malformation. The yield of cardiomyopathy gene panel testing in infants, children, and adolescents with a diagnosis of LVNC is unknown. By characterizing a pediatric population with LVNC, we sought to determine the yield of cardiomyopathy gene panel testing, distinguish the yield of testing for LVNC with or without co-occurring cardiac findings, and define additional factors influencing genetic testing yield. METHODS AND RESULTS: One hundred twenty-eight individuals diagnosed with LVNC at ≤21 years of age were identified, including 59% with idiopathic pathogenesis, 32% with familial disease, and 9% with a syndromic or metabolic diagnosis. Overall, 75 individuals had either cardiomyopathy gene panel (n=65) or known variant testing (n=10). The yield of cardiomyopathy gene panel testing was 9%. The severity of LVNC by imaging criteria was not associated with positive genetic testing, co-occurring cardiac features, pathogenesis, family history, or myocardial dysfunction. Individuals with isolated LVNC were significantly less likely to have a positive genetic testing result compared with those with LVNC and co-occurring cardiomyopathy (0% versus 12%, respectively; P<0.01). CONCLUSIONS: Genetic testing should be considered in individuals with cardiomyopathy co-occurring with LVNC. These data do not suggest an indication for cardiomyopathy gene panel testing in individuals with isolated LVNC in the absence of a family history of cardiomyopathy.
BACKGROUND:Left ventricular noncompaction (LVNC) can occur in isolation or can co-occur with a cardiomyopathy phenotype or cardiovascular malformation. The yield of cardiomyopathy gene panel testing in infants, children, and adolescents with a diagnosis of LVNC is unknown. By characterizing a pediatric population with LVNC, we sought to determine the yield of cardiomyopathy gene panel testing, distinguish the yield of testing for LVNC with or without co-occurring cardiac findings, and define additional factors influencing genetic testing yield. METHODS AND RESULTS: One hundred twenty-eight individuals diagnosed with LVNC at ≤21 years of age were identified, including 59% with idiopathic pathogenesis, 32% with familial disease, and 9% with a syndromic or metabolic diagnosis. Overall, 75 individuals had either cardiomyopathy gene panel (n=65) or known variant testing (n=10). The yield of cardiomyopathy gene panel testing was 9%. The severity of LVNC by imaging criteria was not associated with positive genetic testing, co-occurring cardiac features, pathogenesis, family history, or myocardial dysfunction. Individuals with isolated LVNC were significantly less likely to have a positive genetic testing result compared with those with LVNC and co-occurring cardiomyopathy (0% versus 12%, respectively; P<0.01). CONCLUSIONS: Genetic testing should be considered in individuals with cardiomyopathy co-occurring with LVNC. These data do not suggest an indication for cardiomyopathy gene panel testing in individuals with isolated LVNC in the absence of a family history of cardiomyopathy.
Authors: Stephanie M Ware; Surbhi Bhatnagar; Phillip J Dexheimer; James D Wilkinson; Arthi Sridhar; Xiao Fan; Yufeng Shen; Muhammad Tariq; Jeffrey A Schubert; Steven D Colan; Ling Shi; Charles E Canter; Daphne T Hsu; Neha Bansal; Steven A Webber; Melanie D Everitt; Paul F Kantor; Joseph W Rossano; Elfriede Pahl; Paolo Rusconi; Teresa M Lee; Jeffrey A Towbin; Ashwin K Lal; Wendy K Chung; Erin M Miller; Bruce Aronow; Lisa J Martin; Steven E Lipshultz Journal: Am J Hum Genet Date: 2022-01-12 Impact factor: 11.043
Authors: Sylvia Krupickova; Suzan Hatipoglu; Giovanni DiSalvo; Inga Voges; Daniel Redfearn; Sandrine Foldvari; Christian Eichhorn; Sian Chivers; Filippo Puricelli; Grazia Delle-Donne; Courtney Barth; Dudley J Pennell; Sanjay K Prasad; Piers E F Daubeney Journal: J Cardiovasc Magn Reson Date: 2021-07-08 Impact factor: 5.364