PCICU attending; Director, Pediatric MCS, Pulmonary hypertension; heart failure attending Advocate Children's Heart Institute/University of Chicago Comer Children's Valparaiso, Indiana, United States
Abstract:
Introduction: Pediatric dilated cardiomyopathy (DCM) encompasses a wide range of etiologies, but often leads to heart failure (HF) and remains the most common diagnosis leading to heart transplantation in children. Familial causes of DCM are a relatively uncommon etiology. We present a Jehovah Witness (JW) family with a rare troponin variant resulting in severe, progressive DCM.
Methods: A retrospective review of medical records of family members to delineate etiology and course of DCM was conducted.
Results: Three consecutive children were affected with DCM. The oldest son presented at 32 months of age with severe HF (ejection fraction, EF < 35%), which progressed to EF < 20% over 5 months despite treatment initially with milrinone and then enalapril and carvedilol. He was referred for heart transplant evaluation, however parents declined based on religious reasons with avoidance of blood transfusions. He died 6 months after initial diagnosis from progressive HF. The second oldest son then presented at 17 months of age with severe HF symptoms (EF 28%). Following this second diagnosis, cardiogenetic testing was performed on all living primary family members (figure), revealing two TNN13 (troponin) variants of uncertain significance. Each parent was found to carry a different TNN13 variant and 2 of the 3 living children were found to be compound heterozygous, both of whom developed symptoms. TNN13 is primarily associated with autosomal dominant cardiomyopathy. His parents declined heart transplant evaluation for previously stated reasons. He was transitioned to oral HF medications and discharged to hospice. He died two months after initial presentation from progressive heart failure. The 4-year old daughter positive for the TNNI3 variant later presented with severe HF symptoms (EF 23%). Sixteen months prior, her echocardiogram revealed EF 57% with no left ventricular dilation. The advanced HF team counseled her parents on potential surgical options and worked with JW community leaders to locate a transplant center that would consider attempt at bloodless surgeries. Her HF symptoms rapidly progressed within 2 weeks and she was transferred to a center where a Berlin Heart left ventricular assist device was placed the day after arrival using a blood sparing strategy. She was subsequently transplanted 116 days later and continues to do well more than 1 year post-transplant. An older daughter is clinically unaffected and an infant son born last year does not carry the variant.
Conclusion: Children in this family compound heterozygous for TNN13 variants develop progressive rapid onset of DCM, suggesting an autosomal recessive form of a severe TNN13-related cardiomyopathy. Delineating genetic causes of DCM is vital to identify at-risk family members in a timely manner. Early recognition of ethical and religious considerations that may play a role in decision-making is key to counseling families and identifying opportunities to intervene.
