TY - JOUR
T1 - Familial occurrences of cardiac wild-type transthyretin amyloidosis
T2 - a case series
AU - Westin, Oscar M
AU - Clemmensen, Tor S
AU - Hansen, Anne Tybjærg
AU - Gustafsson, Finn
AU - Poulsen, Steen Hvitfeldt
N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85193728632&partnerID=8YFLogxK
U2 - 10.1093/ehjcr/ytae199
DO - 10.1093/ehjcr/ytae199
M3 - Journal article
C2 - 38765770
SN - 2514-2119
VL - 8
JO - European Heart Journal - Case Reports
JF - European Heart Journal - Case Reports
IS - 5
M1 - ytae199
ER -