Familial occurrences of cardiac wild-type transthyretin amyloidosis: a case series

• Published in: European heart journal : case reports 2024-05, Vol.8 (5), p.ytae199
• Main Authors: Westin, Oscar M, Clemmensen, Tor S, Hansen, Anne Tybjærg, Gustafsson, Finn, Poulsen, Steen Hvitfeldt
• Format: Article
• Language: English
• Subjects: Amyloidosis; Cardiac patients; Case Series; Electrocardiogram; Electrocardiography; Genetic aspects; Genetic screening; Heart failure; Medical research; Medicine, Experimental; Type 2 diabetes
• ISSN: 2514-2119; 2514-2119
• DOI: 10.1093/ehjcr/ytae199

Abstract Background Cardiomyopathy caused by aggregation and deposition of transthyretin amyloid fibrils in the heart (ATTR-CM) is divided into a hereditary (ATTRv) and a wild-type (ATTRwt) forms. While ATTR-CM has been considered a rare disease, recent studies suggest that it is severely underdiagnosed and an important cause of heart failure in elderly patients. Familial occurrence is implicit in ATTRv, but it is not expected in ATTRwt. Case summary We report a case series of two unrelated families each with two brothers diagnosed with ATTRwt. Genetic testing did not reveal mutations in the transthyretin gene. Family screening with electrocardiogram, echocardiography, and genetic testing did not raise any suspicion of ATTR in first-line family members. Discussion Familial occurrence of a rare, non-hereditary disease is statistically unlikely. Two siblings in two different families diagnosed with ATTRwt highlight that the aetiology of ATTRwt is poorly understood, and that genetic factors distinct from mutations in the transthyretin gene, as well as environmental factors, might contribute to the pathogenesis. Identifying such factors might reveal new therapeutic targets. To investigate this further, clinicians need to be aware of the possibility of familial occurrence of ATTRwt.