TY - JOUR
T1 - Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus
AU - Grandis, M.
AU - Obici, L.
AU - Luigetti, M.
AU - Briani, C.
AU - Benedicenti, F.
AU - Bisogni, G.
AU - Canepa, M.
AU - Cappelli, F.
AU - Danesino, C.
AU - Fabrizi, G. M.
AU - Fenu, S.
AU - Ferrandes, G.
AU - Gemelli, C.
AU - Manganelli, F.
AU - Mazzeo, A.
AU - Melchiorri, L.
AU - Perfetto, F.
AU - Pradotto, L. G.
AU - Rimessi, P.
AU - Tini, G.
AU - Tozza, S.
AU - Trevisan, L.
AU - Pareyson, D.
AU - Mandich, P.
N1 - Funding Information:
Independent Health Educational Grant from Pfizer to PM.
Funding Information:
M. Grandis acknowledges donations from Sanofi Genzyme to support research activities of her Research Unit; financial support from Alnylam and Sanofi Genzyme for participation in National and International Meetings; speaker honorarium from Sanofi Genzyme. L. Obici acknowledges speaker and consultation honoraria from Akcea, Alnylam and Pfizer. M. Luigetti received financial grants (honoraria and speaking) from Akcea, Alnylam and Pfizer, and travel grants from Akcea, Alnylam, Pfizer, Kedrion, CSL Behring and Grifols. C. Briani reports speaker and consulting honoraria from Akcea, Alnylam and Pfizer, and travel grants from Kedrion, Alnylam and CSL Behring. G. Bisogni reports financial grants (honoraria and speaking) from Alnylam, travel grants from Alnylam, Pfizer and Grifols. M. Canepa received speaker and advisor fees from Akcea Therapeutics, Menarini, Novartis, Pfizer, Sanofi and Sanofi Genzyme, Vifor Pharma, and an investigator-initiated grant from Pfizer. G. M. Fabrizi was sponsored by Akcea Therapeutics to attend the 2019 American Academy of Neurology Conference in Philadelphia and by Pfizer Inc. to attend the 2018 ARia (Advances and Research in TTR Amyloidosis) VII symposium, in Frankfurt. GMF received fees for Board membership from Akcea Therapeutics (Akcea Scientific Advisory Board, Milan January 29 2019) and Alnylam Pharmaceuticals (Alnylam Scientific Advisory Board, Milan December 11 2019). S. Fenu acknowledges financial support from Alnylam, Akcea and Pfizer for participation in National and International Meetings; participation in Advisory Board of Akcea. C. Gemelli reports grants to attend scientific meetings from Sanofi Genzyme and Pfizer. F. Manganelli received personal fees for scientific events from Alfa-Sigma, Alnylam and Akcea and has received travel grant to attend scientific meeting from CSL Behring. A. Mazzeo reports participation in Advisory Board of Pfizer, Alnylam, Akcea. F. Perfetto received speaker honoraria from Pfizer, Alnylam Pharmaceuticals and Akcea. L.G. Pradotto received financial grants (honoraria and speaking) from Akcea and Alnylam, and travel grants from Akcea, Alnylam, and Pfizer. D. Pareyson acknowledges donations from Pfizer, LAM Therapeutics and Acceleron to support research activities of his Research Unit; financial support from Pfizer, Alnylam and Kedrion for participation in National and International Meetings; participation in Advisory Board of Inflectis, Alnylam and Akcea; speaker honorarium from Alnylam. P. Mandich was sponsored by Independent Health Educational Grant from Pfizer (2018). F. Benedicenti, F. Cappelli, C. Danesino, G. Ferrandes, L. Melchiorri, P. Rimessi, G. Tini, S. Tozza, L. Trevisan have no disclosures.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
AB - Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
KW - Attrv
KW - Hereditary transthyretin amyloidosis
KW - Pre-symptomatic genetic testing; PST
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U2 - 10.1186/s13023-020-01633-z
DO - 10.1186/s13023-020-01633-z
M3 - Article
AN - SCOPUS:85097555700
VL - 15
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
IS - 1
M1 - 348
ER -