Jaap I van Waning1, Kadir Caliskan2, Michelle Michels2, Arend F L Schinkel2, Alexander Hirsch3, Michiel Dalinghaus4, Yvonne M Hoedemaekers5, Marja W Wessels1, Arne S IJpma6, Robert M W Hofstra1, Marjon A van Slegtenhorst1, Danielle Majoor-Krakauer7. 1. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands. 2. Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands. 3. Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands. 4. Department of Pediatrics, Erasmus Medical Center, Rotterdam, the Netherlands. 5. Department of Clinical Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 6. Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands. 7. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: d.majoor-krakauer@erasmusmc.nl.
Abstract
BACKGROUND: There is overlap in genetic causes and cardiac features in noncompaction cardiomyopathy (NCCM), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM). OBJECTIVES: The goal of this study was to predict phenotype and outcome in relatives according to the clinical features and genotype of NCCM index cases. METHODS: Retrospective DNA and cardiac screening of relatives of 113 families from 143 index patients were used to classify NCCM cases according to the cardiac phenotype. These cases were classified as isolated NCCM, NCCM with left ventricular (LV) dilation (DCM), and NCCM with LV hypertrophy (HCM). RESULTS: In 58 (51%) families, screening identified 73 relatives with NCCM and 34 with DCM or HCM without NCCM. The yield of family screening was higher in families with a mutation (p < 0.001). Fifty-four families had a mutation. Nonpenetrance was observed in 37% of the relatives with a mutation. Index cases were more often symptomatic than affected relatives (p < 0.001). NCCM with DCM (53%) was associated with LV systolic dysfunction (p < 0.001), increased risk for major adverse cardiac events, mutations in the tail of MYH7 (p < 0.001), and DCM without NCCM in relatives (p < 0.001). Isolated NCCM (43%) was associated with a milder course, mutations in the head of MYH7, asymptomatic NCCM (42%) (p = 0.018), and isolated NCCM in relatives (p = 0.004). NCCM with HCM (4%) was associated with MYBPC3 and HCM without NCCM in relatives (p < 0.001). CONCLUSIONS: The phenotype of relatives may be predicted according to the NCCM phenotype and the mutation of index patients. NCCM phenotypes were related to outcome. In this way, clinical and genetic features of index patients may help prediction of outcome in relatives.
BACKGROUND: There is overlap in genetic causes and cardiac features in noncompaction cardiomyopathy (NCCM), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM). OBJECTIVES: The goal of this study was to predict phenotype and outcome in relatives according to the clinical features and genotype of NCCM index cases. METHODS: Retrospective DNA and cardiac screening of relatives of 113 families from 143 index patients were used to classify NCCM cases according to the cardiac phenotype. These cases were classified as isolated NCCM, NCCM with left ventricular (LV) dilation (DCM), and NCCM with LV hypertrophy (HCM). RESULTS: In 58 (51%) families, screening identified 73 relatives with NCCM and 34 with DCM or HCM without NCCM. The yield of family screening was higher in families with a mutation (p < 0.001). Fifty-four families had a mutation. Nonpenetrance was observed in 37% of the relatives with a mutation. Index cases were more often symptomatic than affected relatives (p < 0.001). NCCM with DCM (53%) was associated with LV systolic dysfunction (p < 0.001), increased risk for major adverse cardiac events, mutations in the tail of MYH7 (p < 0.001), and DCM without NCCM in relatives (p < 0.001). Isolated NCCM (43%) was associated with a milder course, mutations in the head of MYH7, asymptomatic NCCM (42%) (p = 0.018), and isolated NCCM in relatives (p = 0.004). NCCM with HCM (4%) was associated with MYBPC3 and HCM without NCCM in relatives (p < 0.001). CONCLUSIONS: The phenotype of relatives may be predicted according to the NCCM phenotype and the mutation of index patients. NCCM phenotypes were related to outcome. In this way, clinical and genetic features of index patients may help prediction of outcome in relatives.
Authors: Perry Wengrofsky; Christopher Armenia; Filip Oleszak; Eric Kupferstein; Chandra Rednam; Cristina A Mitre; Samy I McFarlane Journal: EC Clin Exp Anat Date: 2019-07-29
Authors: Rabia S Khan; Elfriede Pahl; Lisa Dellefave-Castillo; Karen Rychlik; Alexander Ing; Kai Lee Yap; Casey Brew; Jamie R Johnston; Elizabeth M McNally; Gregory Webster Journal: J Am Heart Assoc Date: 2021-12-22 Impact factor: 5.501